LIVIVO - Search results -

Search results

Result 1 - 10 of total 13

Search options

Article ; Online: Acid ceramidase improves mitochondrial function and oxidative stress in Niemann-Pick type C disease by repressing STARD1 expression and mitochondrial cholesterol accumulation.

Torres, Sandra / Solsona-Vilarrasa, Estel / Nuñez, Susana / Matías, Nuria / Insausti-Urkia, Naroa / Castro, Fernanda / Casasempere, Mireia / Fabriás, Gemma / Casas, Josefina / Enrich, Carlos / Fernández-Checa, José C / Garcia-Ruiz, Carmen

Redox biology

2021 Volume 45, Page(s) 102052

Abstract: Niemann-Pick type C (NPC) disease, a lysosomal storage disorder caused by defective NPC1/NPC2 function, results in the accumulation of cholesterol and glycosphingolipids in lysosomes of affected organs, such as liver and brain. Moreover, increase of ... ...

Abstract	Niemann-Pick type C (NPC) disease, a lysosomal storage disorder caused by defective NPC1/NPC2 function, results in the accumulation of cholesterol and glycosphingolipids in lysosomes of affected organs, such as liver and brain. Moreover, increase of mitochondrial cholesterol (mchol) content and impaired mitochondrial function and GSH depletion contribute to NPC disease. However, the underlying mechanism of mchol accumulation in NPC disease remains unknown. As STARD1 is crucial in intramitochondrial cholesterol trafficking and acid ceramidase (ACDase) has been shown to regulate STARD1, we explored the functional relationship between ACDase and STARD1 in NPC disease. Liver and brain of Npc1
MeSH term(s)	Acid Ceramidase/metabolism ; Animals ; Cholesterol/metabolism ; Humans ; Lysosomes/metabolism ; Mice ; Mice, Knockout ; Mitochondria/metabolism ; Niemann-Pick Disease, Type C/genetics ; Niemann-Pick Disease, Type C/metabolism ; Oxidative Stress ; Phosphoproteins/metabolism
Chemical Substances	Phosphoproteins ; steroidogenic acute regulatory protein ; Cholesterol (97C5T2UQ7J) ; Acid Ceramidase (EC 3.5.1.23)
Language	English
Publishing date	2021-06-19
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2701011-9
ISSN	2213-2317 ; 2213-2317
ISSN (online)	2213-2317
ISSN	2213-2317
DOI	10.1016/j.redox.2021.102052
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: MLN64 induces mitochondrial dysfunction associated with increased mitochondrial cholesterol content.

Balboa, Elisa / Castro, Juan / Pinochet, María-José / Cancino, Gonzalo I / Matías, Nuria / Sáez, P J / Martínez, Alexis / Álvarez, Alejandra R / Garcia-Ruiz, Carmen / Fernandez-Checa, José C / Zanlungo, Silvana

Redox biology

2017 Volume 12, Page(s) 274–284

Abstract: MLN64 is a late endosomal cholesterol-binding membrane protein that has been implicated in cholesterol transport from endosomal membranes to the plasma membrane and/or mitochondria, in toxin-induced resistance, and in mitochondrial dysfunction. Down- ... ...

Abstract	MLN64 is a late endosomal cholesterol-binding membrane protein that has been implicated in cholesterol transport from endosomal membranes to the plasma membrane and/or mitochondria, in toxin-induced resistance, and in mitochondrial dysfunction. Down-regulation of MLN64 in Niemann-Pick C1 deficient cells decreased mitochondrial cholesterol content, suggesting that MLN64 functions independently of NPC1. However, the role of MLN64 in the maintenance of endosomal cholesterol flow and intracellular cholesterol homeostasis remains unclear. We have previously described that hepatic MLN64 overexpression increases liver cholesterol content and induces liver damage. Here, we studied the function of MLN64 in normal and NPC1-deficient cells and we evaluated whether MLN64 overexpressing cells exhibit alterations in mitochondrial function. We used recombinant-adenovirus-mediated MLN64 gene transfer to overexpress MLN64 in mouse liver and hepatic cells; and RNA interference to down-regulate MLN64 in NPC1-deficient cells. In MLN64-overexpressing cells, we found increased mitochondrial cholesterol content and decreased glutathione (GSH) levels and ATPase activity. Furthermore, we found decreased mitochondrial membrane potential and mitochondrial fragmentation and increased mitochondrial superoxide levels in MLN64-overexpressing cells and in NPC1-deficient cells. Consequently, MLN64 expression was increased in NPC1-deficient cells and reduction of its expression restore mitochondrial membrane potential and mitochondrial superoxide levels. Our findings suggest that MLN64 overexpression induces an increase in mitochondrial cholesterol content and consequently a decrease in mitochondrial GSH content leading to mitochondrial dysfunction. In addition, we demonstrate that MLN64 expression is increased in NPC cells and plays a key role in cholesterol transport into the mitochondria.
MeSH term(s)	Animals ; CHO Cells ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Cholesterol/metabolism ; Cricetulus ; Dependovirus/genetics ; Genetic Vectors/administration & dosage ; Glutathione/metabolism ; Hep G2 Cells ; Humans ; Liver/cytology ; Liver/metabolism ; Membrane Potential, Mitochondrial ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mice ; Mitochondria/metabolism ; Mitochondria/physiology ; Niemann-Pick Diseases/genetics ; Niemann-Pick Diseases/metabolism ; Niemann-Pick Diseases/physiopathology ; Superoxides/metabolism
Chemical Substances	Carrier Proteins ; Membrane Proteins ; STARD3 protein, human ; Superoxides (11062-77-4) ; Cholesterol (97C5T2UQ7J) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2017-03-02
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2213-2317
ISSN (online)	2213-2317
DOI	10.1016/j.redox.2017.02.024
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: The 2-oxoglutarate carrier promotes liver cancer by sustaining mitochondrial GSH despite cholesterol loading.

Baulies, Anna / Montero, Joan / Matías, Nuria / Insausti, Naroa / Terrones, Oihana / Basañez, Gorka / Vallejo, Carmen / Conde de La Rosa, Laura / Martinez, Laura / Robles, David / Morales, Albert / Abian, Joaquin / Carrascal, Montserrat / Machida, Keigo / Kumar, Dinesh B U / Tsukamoto, Hidekazu / Kaplowitz, Neil / Garcia-Ruiz, Carmen / Fernández-Checa, José C

Redox biology

2017 Volume 14, Page(s) 164–177

Abstract: Cancer cells exhibit mitochondrial cholesterol (mt-cholesterol) accumulation, which contributes to cell death resistance by antagonizing mitochondrial outer membrane (MOM) permeabilization. Hepatocellular mt-cholesterol loading, however, promotes ... ...

Abstract	Cancer cells exhibit mitochondrial cholesterol (mt-cholesterol) accumulation, which contributes to cell death resistance by antagonizing mitochondrial outer membrane (MOM) permeabilization. Hepatocellular mt-cholesterol loading, however, promotes steatohepatitis, an advanced stage of chronic liver disease that precedes hepatocellular carcinoma (HCC), by depleting mitochondrial GSH (mGSH) due to a cholesterol-mediated impairment in mGSH transport. Whether and how HCC cells overcome the restriction of mGSH transport imposed by mt-cholesterol loading to support mGSH uptake remains unknown. Although the transport of mGSH is not fully understood, SLC25A10 (dicarboxylate carrier, DIC) and SLC25A11 (2-oxoglutarate carrier, OGC) have been involved in mGSH transport, and therefore we examined their expression and role in HCC. Unexpectedly, HCC cells and liver explants from patients with HCC exhibit divergent expression of these mitochondrial carriers, with selective OGC upregulation, which contributes to mGSH maintenance. OGC but not DIC downregulation by siRNA depleted mGSH levels and sensitized HCC cells to hypoxia-induced ROS generation and cell death as well as impaired cell growth in three-dimensional multicellular HCC spheroids, effects that were reversible upon mGSH replenishment by GSH ethyl ester, a membrane permeable GSH precursor. We also show that OGC regulates mitochondrial respiration and glycolysis. Moreover, OGC silencing promoted hypoxia-induced cardiolipin peroxidation, which reversed the inhibition of cholesterol on the permeabilization of MOM-like liposomes induced by Bax or Bak. Genetic OGC knockdown reduced the ability of tumor-initiating stem-like cells to induce liver cancer. These findings underscore the selective overexpression of OGC as an adaptive mechanism of HCC to provide adequate mGSH levels in the face of mt-cholesterol loading and suggest that OGC may be a novel therapeutic target for HCC treatment.
MeSH term(s)	Animals ; Cell Line, Tumor ; Cell Proliferation ; Cholesterol/metabolism ; Dicarboxylic Acid Transporters/antagonists & inhibitors ; Dicarboxylic Acid Transporters/genetics ; Dicarboxylic Acid Transporters/metabolism ; Glutathione/metabolism ; Hep G2 Cells ; Humans ; Liver/metabolism ; Liver/pathology ; Liver Neoplasms/drug therapy ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology ; Male ; Membrane Transport Proteins/chemistry ; Membrane Transport Proteins/genetics ; Membrane Transport Proteins/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mitochondria/metabolism ; Mitochondria/pathology ; Mitochondrial Membranes/metabolism ; Oxidative Stress ; RNA, Small Interfering/metabolism ; RNA, Small Interfering/therapeutic use ; Rats
Chemical Substances	Dicarboxylic Acid Transporters ; Membrane Transport Proteins ; RNA, Small Interfering ; oxoglutarate translocator ; Cholesterol (97C5T2UQ7J) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2017-09-14
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701011-9
ISSN	2213-2317 ; 2213-2317
ISSN (online)	2213-2317
ISSN	2213-2317
DOI	10.1016/j.redox.2017.08.022
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Mitochondrial S-adenosyl-L-methionine transport is insensitive to alcohol-mediated changes in membrane dynamics.

Fernández, Anna / Colell, Anna / Caballero, Francisco / Matías, Nuria / García-Ruiz, Carmen / Fernández-Checa, José C

Alcoholism, clinical and experimental research

2009 Volume 33, Issue 7, Page(s) 1169–1180

Abstract: Background: Alcohol-induced liver injury is associated with decreased S-adenosyl-l-methionine (SAM)/S-adenosyl-l-homocysteine (SAH) ratio and mitochondrial glutathione (mGSH) depletion, which has been shown to sensitize hepatocytes to tumor necrosis ... ...

Abstract	Background: Alcohol-induced liver injury is associated with decreased S-adenosyl-l-methionine (SAM)/S-adenosyl-l-homocysteine (SAH) ratio and mitochondrial glutathione (mGSH) depletion, which has been shown to sensitize hepatocytes to tumor necrosis factor (TNF). Aims: As the effect of alcohol on mitochondrial SAM (mSAM) has been poorly characterized, our aim was to examine the status and transport of mSAM in relation to that of mGSH during alcohol intake. Methods: Sprague-Dawley rats were pair fed Lieber-DeCarli diets containing alcohol for 1 to 4 weeks and liver fractionated into cytosol and mitochondria to examine the mSAM transport and its sensitivity to membrane dynamics. Results: We found that cytosol SAM was depleted from the first week of alcohol feeding, with mSAM levels paralleling these changes. Cytosol SAH, however, increased during the first 3 weeks of alcohol intake, whereas its mitochondrial levels remained unchanged. mGSH depletion occurred by 3 to 4 weeks of alcohol intake due to cholesterol-mediated impaired transport from the cytosol. In contrast to this outcome, the transport of SAM into hepatic mitochondria was unaffected by alcohol intake and resistant to cholesterol-mediated perturbations in membrane dynamics; furthermore cytosolic SAH accumulation in primary hepatocytes by SAH hydrolase inhibition reproduced the mSAM depletion by alcohol due to the competition of SAH with SAM for mitochondrial transport. However, alcohol feeding did not potentiate the sensitivity to inhibition by SAH accumulation. Conclusions: Alcohol-induced mSAM depletion precedes that of mGSH and occurs independently of alcohol-mediated perturbations in membrane dynamics, disproving an inherent defect in the mSAM transport by alcohol. These findings suggest that the early mSAM depletion may contribute to the alterations of mitochondrial membrane dynamics and the subsequent mGSH down-regulation induced by alcohol feeding.
MeSH term(s)	Animals ; Biological Transport, Active/drug effects ; Biological Transport, Active/physiology ; Cell Membrane/drug effects ; Cell Membrane/metabolism ; Cells, Cultured ; Ethanol/administration & dosage ; Mitochondria, Liver/drug effects ; Mitochondria, Liver/metabolism ; Rats ; Rats, Sprague-Dawley ; S-Adenosylmethionine/metabolism ; Time Factors
Chemical Substances	Ethanol (3K9958V90M) ; S-Adenosylmethionine (7LP2MPO46S)
Language	English
Publishing date	2009-07
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	428999-7
ISSN	1530-0277 ; 0145-6008
ISSN (online)	1530-0277
ISSN	0145-6008
DOI	10.1111/j.1530-0277.2009.00940.x
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1375: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: Specific Contribution of Methionine and Choline in Nutritional Nonalcoholic Steatohepatitis: IMPACT ON MITOCHONDRIAL S-ADENOSYL-L-METHIONINE AND GLUTATHIONE

Caballero, Francisco / Fernández, Anna / Matías, Nuria / Martínez, Laura / Fucho, Raquel / Elena, Montserrat / Caballeria, Joan / Morales, Albert / Fernández-Checa, José C / García-Ruiz, Carmen

Journal of biological chemistry. 2010 June 11, v. 285, no. 24

2010

Abstract: The pathogenesis and treatment of nonalcoholic steatohepatitis (NASH) are not well established. Feeding a diet deficient in both methionine and choline (MCD) is one of the most common models of NASH, which is characterized by steatosis, mitochondrial ... ...

Abstract	The pathogenesis and treatment of nonalcoholic steatohepatitis (NASH) are not well established. Feeding a diet deficient in both methionine and choline (MCD) is one of the most common models of NASH, which is characterized by steatosis, mitochondrial dysfunction, hepatocellular injury, oxidative stress, inflammation, and fibrosis. However, the individual contribution of the lack of methionine and choline in liver steatosis, advanced pathology and impact on mitochondrial S-adenosyl-L-methionine (SAM) and glutathione (GSH), known regulators of disease progression, has not been specifically addressed. Here, we examined the regulation of mitochondrial SAM and GSH and signs of disease in mice fed a MCD, methionine-deficient (MD), or choline-deficient (CD) diet. The MD diet reproduced most of the deleterious effects of MCD feeding, including weight loss, hepatocellular injury, oxidative stress, inflammation, and fibrosis, whereas CD feeding was mainly responsible for steatosis, characterized by triglycerides and free fatty acids accumulation. These findings were preceded by MCD- or MD-mediated SAM and GSH depletion in mitochondria due to decreased mitochondrial membrane fluidity associated with a lower phosphatidylcholine/phosphatidylethanolamine ratio. MCD and MD but not CD feeding resulted in increased ceramide levels by acid sphingomyelinase. Moreover, GSH ethyl ester or SAM therapy restored mitochondrial GSH and ameliorated hepatocellular injury in mice fed a MCD or MD diet. Thus, the depletion of SAM and GSH in mitochondria is an early event in the MCD model of NASH, which is determined by the lack of methionine. Moreover, therapy using permeable GSH prodrugs may be of relevance in NASH.
Language	English
Dates of publication	2010-0611
Size	p. 18528-18536.
Publishing place	American Society for Biochemistry and Molecular Biology
Document type	Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Bonn / Germany

Z 4' 65/118: Show issues
Z 6.2: Show issues

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Mitochondrial GSH replenishment as a potential therapeutic approach for Niemann Pick type C disease.

Torres, Sandra / Matías, Nuria / Baulies, Anna / Nuñez, Susana / Alarcon-Vila, Cristina / Martinez, Laura / Nuño, Natalia / Fernandez, Anna / Caballeria, Joan / Levade, Thierry / Gonzalez-Franquesa, Alba / Garcia-Rovés, Pablo / Balboa, Elisa / Zanlungo, Silvana / Fabrías, Gemma / Casas, Josefina / Enrich, Carlos / Garcia-Ruiz, Carmen / Fernández-Checa, José C

Redox biology

2016 Volume 11, Page(s) 60–72

Abstract: Niemann Pick type C (NPC) disease is a progressive lysosomal storage disorder caused by mutations in genes encoding NPC1/NPC2 proteins, characterized by neurological defects, hepatosplenomegaly and premature death. While the primary biochemical feature ... ...

Abstract	Niemann Pick type C (NPC) disease is a progressive lysosomal storage disorder caused by mutations in genes encoding NPC1/NPC2 proteins, characterized by neurological defects, hepatosplenomegaly and premature death. While the primary biochemical feature of NPC disease is the intracellular accumulation of cholesterol and gangliosides, predominantly in endolysosomes, mitochondrial cholesterol accumulation has also been reported. As accumulation of cholesterol in mitochondria is known to impair the transport of GSH into mitochondria, resulting in mitochondrial GSH (mGSH) depletion, we investigated the impact of mGSH recovery in NPC disease. We show that GSH ethyl ester (GSH-EE), but not N-acetylcysteine (NAC), restored the mGSH pool in liver and brain of Npc1
MeSH term(s)	Acetylcysteine/metabolism ; Animals ; Cerebellum/metabolism ; Cerebellum/pathology ; Cholesterol/metabolism ; Glutathione/metabolism ; Glutathione/pharmacology ; Humans ; Intracellular Signaling Peptides and Proteins ; Lysosomes/genetics ; Lysosomes/metabolism ; Mice ; Mice, Knockout ; Mitochondria/metabolism ; Mitochondria/pathology ; Mutation ; Niemann-Pick C1 Protein ; Niemann-Pick Disease, Type C/genetics ; Niemann-Pick Disease, Type C/metabolism ; Niemann-Pick Disease, Type C/pathology ; Oxidative Phosphorylation ; Proteins/genetics ; Proteins/metabolism ; Purkinje Cells/metabolism ; Vesicular Transport Proteins/genetics ; Vesicular Transport Proteins/metabolism
Chemical Substances	Intracellular Signaling Peptides and Proteins ; Niemann-Pick C1 Protein ; Npc1 protein, mouse ; Npc2 protein, mouse ; Proteins ; Vesicular Transport Proteins ; Cholesterol (97C5T2UQ7J) ; Glutathione (GAN16C9B8O) ; Acetylcysteine (WYQ7N0BPYC)
Language	English
Publishing date	2016-11-20
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2701011-9
ISSN	2213-2317 ; 2213-2317
ISSN (online)	2213-2317
ISSN	2213-2317
DOI	10.1016/j.redox.2016.11.010
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Targeting cholesterol at different levels in the mevalonate pathway protects fatty liver against ischemia-reperfusion injury.

Llacuna, Laura / Fernández, Anna / Montfort, Claudia Von / Matías, Núria / Martínez, Laura / Caballero, Francisco / Rimola, Antoni / Elena, Montserrat / Morales, Albert / Fernández-Checa, José C / García-Ruiz, Carmen

Journal of hepatology

2011 Volume 54, Issue 5, Page(s) 1002–1010

Abstract: Background & aims: Liver steatosis enhances ischemia/reperfusion (I/R) injury and is considered a primary factor in graft failure after liver transplantation. Although previous reports have shown a role for qualitative steatosis (macrovesicular vs. ... ...

Abstract	Background & aims: Liver steatosis enhances ischemia/reperfusion (I/R) injury and is considered a primary factor in graft failure after liver transplantation. Although previous reports have shown a role for qualitative steatosis (macrovesicular vs. microvesicular) in hepatic I/R injury, no studies have compared side by side the specific contribution of individual lipids accumulating in fatty liver to I/R damage. Methods: We used nutritional and genetic models of micro and macrovesicular fatty livers exhibiting specific lipid profiles to assess their susceptibility to normothermic I/R injury. Results: Unlike choline-deficient (CD) diet-fed mice, characterized by predominant liver triglycerides/free fatty acids (TG/FFA) accumulation, mice fed a cholesterol-enriched (HC) diet, which exhibited enhanced hepatic cholesterol loading in mitochondria, were highly sensitive to I/R-induced liver injury. In vivo two-photon confocal imaging revealed enhanced mitochondrial depolarization and generation of reactive oxygen species following hepatic I/R in HC-fed but not in CD-fed mice, consistent with decreased mitochondrial GSH (mGSH) observed in HC-fed mice. Moreover, ob/ob mice, characterized by increased hepatic TG, FFA, and cholesterol levels, were as sensitive to I/R-mediated liver injury as mice fed the HC diet. Livers from ob/ob mice displayed increased StAR expression and mitochondrial cholesterol accumulation, resulting in mGSH depletion. Interestingly, atorvastatin therapy or squalene synthase inhibition in vivo attenuated StAR overexpression, mitochondrial cholesterol loading, and mGSH depletion, protecting ob/ob mice from I/R-mediated liver injury. Conclusions: Cholesterol accumulation, particularly in mitochondria, sensitizes to hepatic I/R injury, and thus represents a novel target to prevent the enhanced damage of steatotic livers to I/R-mediated damage.
MeSH term(s)	Animals ; Anticholesteremic Agents/pharmacology ; Atorvastatin Calcium ; Cholesterol, Dietary/pharmacokinetics ; Choline/pharmacology ; Choline Deficiency/drug therapy ; Choline Deficiency/metabolism ; Disease Models, Animal ; Disease Susceptibility ; Enzyme Inhibitors/pharmacology ; Farnesyl-Diphosphate Farnesyltransferase/antagonists & inhibitors ; Fatty Liver/drug therapy ; Fatty Liver/metabolism ; Fatty Liver/pathology ; Glutathione/metabolism ; Heptanoic Acids/pharmacology ; Lipotropic Agents/pharmacology ; Liver/drug effects ; Liver/metabolism ; Liver/pathology ; Male ; Mevalonic Acid/metabolism ; Mice ; Mice, Inbred C57BL ; Mitochondria/metabolism ; Obesity/metabolism ; Obesity/pathology ; Pyrroles/pharmacology ; Quinuclidines/pharmacology ; Reperfusion Injury/drug therapy ; Reperfusion Injury/metabolism ; Reperfusion Injury/prevention & control
Chemical Substances	Anticholesteremic Agents ; Cholesterol, Dietary ; Enzyme Inhibitors ; Heptanoic Acids ; Lipotropic Agents ; Pyrroles ; Quinuclidines ; YM 53601 ; Atorvastatin Calcium (48A5M73Z4Q) ; Farnesyl-Diphosphate Farnesyltransferase (EC 2.5.1.21) ; Glutathione (GAN16C9B8O) ; Choline (N91BDP6H0X) ; Mevalonic Acid (S5UOB36OCZ)
Language	English
Publishing date	2011-05
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	605953-3
ISSN	1600-0641 ; 0168-8278
ISSN (online)	1600-0641
ISSN	0168-8278
DOI	10.1016/j.jhep.2010.08.031
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2027: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Specific contribution of methionine and choline in nutritional nonalcoholic steatohepatitis: impact on mitochondrial S-adenosyl-L-methionine and glutathione.

Caballero, Francisco / Fernández, Anna / Matías, Nuria / Martínez, Laura / Fucho, Raquel / Elena, Montserrat / Caballeria, Joan / Morales, Albert / Fernández-Checa, José C / García-Ruiz, Carmen

The Journal of biological chemistry

2010 Volume 285, Issue 24, Page(s) 18528–18536

Abstract	The pathogenesis and treatment of nonalcoholic steatohepatitis (NASH) are not well established. Feeding a diet deficient in both methionine and choline (MCD) is one of the most common models of NASH, which is characterized by steatosis, mitochondrial dysfunction, hepatocellular injury, oxidative stress, inflammation, and fibrosis. However, the individual contribution of the lack of methionine and choline in liver steatosis, advanced pathology and impact on mitochondrial S-adenosyl-L-methionine (SAM) and glutathione (GSH), known regulators of disease progression, has not been specifically addressed. Here, we examined the regulation of mitochondrial SAM and GSH and signs of disease in mice fed a MCD, methionine-deficient (MD), or choline-deficient (CD) diet. The MD diet reproduced most of the deleterious effects of MCD feeding, including weight loss, hepatocellular injury, oxidative stress, inflammation, and fibrosis, whereas CD feeding was mainly responsible for steatosis, characterized by triglycerides and free fatty acids accumulation. These findings were preceded by MCD- or MD-mediated SAM and GSH depletion in mitochondria due to decreased mitochondrial membrane fluidity associated with a lower phosphatidylcholine/phosphatidylethanolamine ratio. MCD and MD but not CD feeding resulted in increased ceramide levels by acid sphingomyelinase. Moreover, GSH ethyl ester or SAM therapy restored mitochondrial GSH and ameliorated hepatocellular injury in mice fed a MCD or MD diet. Thus, the depletion of SAM and GSH in mitochondria is an early event in the MCD model of NASH, which is determined by the lack of methionine. Moreover, therapy using permeable GSH prodrugs may be of relevance in NASH.
MeSH term(s)	Animal Feed ; Animals ; Ceramides/chemistry ; Choline/chemistry ; Fatty Liver/metabolism ; Glutathione/chemistry ; Inflammation ; Lipids/chemistry ; Male ; Methionine/chemistry ; Mice ; Mice, Inbred C57BL ; Mitochondria/metabolism ; Prodrugs/chemistry ; S-Adenosylmethionine/chemistry ; Sphingomyelin Phosphodiesterase/chemistry
Chemical Substances	Ceramides ; Lipids ; Prodrugs ; S-Adenosylmethionine (7LP2MPO46S) ; Methionine (AE28F7PNPL) ; acid sphingomyelinase-1 (EC 3.1.4.-) ; Sphingomyelin Phosphodiesterase (EC 3.1.4.12) ; Glutathione (GAN16C9B8O) ; Choline (N91BDP6H0X)
Language	English
Publishing date	2010-04-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M109.099333
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.108: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Mitochondrial GSH determines the toxic or therapeutic potential of superoxide scavenging in steatohepatitis.

von Montfort, Claudia / Matias, Núria / Fernandez, Anna / Fucho, Raquel / Conde de la Rosa, Laura / Martinez-Chantar, Maria Luz / Mato, José M / Machida, Keigo / Tsukamoto, Hidekazu / Murphy, Michael P / Mansouri, Abdellah / Kaplowitz, Neil / Garcia-Ruiz, Carmen / Fernandez-Checa, Jose C

Journal of hepatology

2012 Volume 57, Issue 4, Page(s) 852–859

Abstract: Background & aims: Steatohepatitis (SH) is associated with mitochondrial dysfunction and excessive production of superoxide, which can then be converted into H(2)O(2) by SOD2. Since mitochondrial GSH (mGSH) plays a critical role in H(2)O(2) reduction, ... ...

Abstract	Background & aims: Steatohepatitis (SH) is associated with mitochondrial dysfunction and excessive production of superoxide, which can then be converted into H(2)O(2) by SOD2. Since mitochondrial GSH (mGSH) plays a critical role in H(2)O(2) reduction, we explored the interplay between superoxide, H(2)O(2), and mGSH in nutritional and genetic models of SH, which exhibit mGSH depletion. Methods: We used isolated mitochondria and primary hepatocytes, as well as in vivo SH models showing mGSH depletion to test the consequences of superoxide scavenging. Results: In isolated mitochondria and primary hepatocytes, superoxide scavenging by SOD mimetics or purified SOD decreased superoxide and peroxynitrite generation but increased H(2)O(2) following mGSH depletion, despite mitochondrial peroxiredoxin/thioredoxin defense. Selective mGSH depletion sensitized hepatocytes to cell death induced by SOD mimetics, and this was prevented by RIP1 kinase inhibition with necrostatin-1 or GSH repletion with GSH ethyl ester (GSHee). Mice fed the methionine-choline deficient (MCD) diet or MAT1A(-/-) mice exhibited reduced SOD2 activity; in vivo treatment with SOD mimetics increased liver damage, inflammation, and fibrosis, despite a decreased superoxide and 3-nitrotyrosine immunoreactivity, effects that were ameliorated by mGSH replenishment with GSHee, but not NAC. As a proof-of-principle of the detrimental role of superoxide scavenging when mGSH was depleted transgenic mice overexpressing SOD2 exhibited enhanced susceptibility to MCD-mediated SH. Conclusions: These findings underscore a critical role for mGSH in the therapeutic potential of superoxide scavenging in SH, and suggest that the combined approach of superoxide scavenging with mGSH replenishment may be important in SH.
MeSH term(s)	Alanine Transaminase/blood ; Animals ; Antimycin A/pharmacology ; Apoptosis ; Choline Deficiency/complications ; Diet ; Disease Models, Animal ; Fatty Liver/blood ; Fatty Liver/enzymology ; Fatty Liver/metabolism ; Free Radical Scavengers/pharmacology ; Glutathione/metabolism ; Hepatocytes/enzymology ; Hepatocytes/metabolism ; Hydrogen Peroxide/metabolism ; Male ; Metalloporphyrins/pharmacology ; Methionine/deficiency ; Methionine Adenosyltransferase/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Mitochondria, Liver/enzymology ; Mitochondria, Liver/metabolism ; Oxidation-Reduction/drug effects ; Pentanoic Acids/pharmacology ; Peroxiredoxin III/metabolism ; Primary Cell Culture ; Reactive Oxygen Species/metabolism ; Superoxide Dismutase/genetics ; Superoxide Dismutase/metabolism ; Superoxides/metabolism ; Thioredoxins/metabolism
Chemical Substances	Free Radical Scavengers ; Metalloporphyrins ; Pentanoic Acids ; Prdx3 protein, mouse ; Reactive Oxygen Species ; Txn2 protein, mouse ; manganese(III)-tetrakis(4-benzoic acid)porphyrin ; Superoxides (11062-77-4) ; 3-hydroxy-4-pentenoic acid (38996-03-1) ; Thioredoxins (52500-60-4) ; Antimycin A (642-15-9) ; Methionine (AE28F7PNPL) ; Hydrogen Peroxide (BBX060AN9V) ; Peroxiredoxin III (EC 1.11.1.15) ; Superoxide Dismutase (EC 1.15.1.1) ; superoxide dismutase 2 (EC 1.15.1.1) ; Mat1a protein, mouse (EC 2.5.1.6) ; Methionine Adenosyltransferase (EC 2.5.1.6) ; Alanine Transaminase (EC 2.6.1.2) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2012-06-09
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	605953-3
ISSN	1600-0641 ; 0168-8278
ISSN (online)	1600-0641
ISSN	0168-8278
DOI	10.1016/j.jhep.2012.05.024
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2027: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: ASMase is required for chronic alcohol induced hepatic endoplasmic reticulum stress and mitochondrial cholesterol loading.

Journal of hepatology

2013 Volume 59, Issue 4, Page(s) 805–813

Abstract: Background & aims: The pathogenesis of alcohol-induced liver disease (ALD) is poorly understood. Here, we examined the role of acid sphingomyelinase (ASMase) in alcohol induced hepatic endoplasmic reticulum (ER) stress, a key mechanism of ALD.: ... ...

Abstract	Background & aims: The pathogenesis of alcohol-induced liver disease (ALD) is poorly understood. Here, we examined the role of acid sphingomyelinase (ASMase) in alcohol induced hepatic endoplasmic reticulum (ER) stress, a key mechanism of ALD. Methods: We examined ER stress, lipogenesis, hyperhomocysteinemia, mitochondrial cholesterol (mChol) trafficking and susceptibility to LPS and concanavalin-A in ASMase(-)(/-) mice fed alcohol. Results: Alcohol feeding increased SREBP-1c, DGAT-2, and FAS mRNA in ASMase(+/+) but not in ASMase(-/-) mice. Compared to ASMase(+/+) mice, ASMase(-/-) mice exhibited decreased expression of ER stress markers induced by alcohol, but the level of tunicamycin-mediated upregulation of ER stress markers and steatosis was similar in both types of mice. The increase in homocysteine levels induced by alcohol feeding was comparable in both ASMase(+/+) and ASMase(-/-) mice. Exogenous ASMase, but not neutral SMase, induced ER stress by perturbing ER Ca(2+) homeostasis. Moreover, alcohol-induced mChol loading and StARD1 overexpression were blunted in ASMase(-/-) mice. Tunicamycin upregulated StARD1 expression and this outcome was abrogated by tauroursodeoxycholic acid. Alcohol-induced liver injury and sensitization to LPS and concanavalin-A were prevented in ASMase(-/-) mice. These effects were reproduced in alcohol-fed TNFR1/R2(-/-) mice. Moreover, ASMase does not impair hepatic regeneration following partial hepatectomy. Of relevance, liver samples from patients with alcoholic hepatitis exhibited increased expression of ASMase, StARD1, and ER stress markers. Conclusions: Our data indicate that ASMase is critical for alcohol-induced ER stress, and provide a rationale for further clinical investigation in ALD.
MeSH term(s)	Amitriptyline/pharmacology ; Animals ; Cholesterol/metabolism ; Disease Models, Animal ; Endoplasmic Reticulum Stress/drug effects ; Hepatitis, Alcoholic/etiology ; Hepatitis, Alcoholic/metabolism ; Hepatitis, Alcoholic/pathology ; Humans ; Hyperhomocysteinemia/complications ; Liver Diseases, Alcoholic/etiology ; Liver Diseases, Alcoholic/metabolism ; Liver Diseases, Alcoholic/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria, Liver/metabolism ; N-Terminal Acetyltransferase A/metabolism ; N-Terminal Acetyltransferase E/metabolism ; Sphingomyelin Phosphodiesterase/deficiency ; Sphingomyelin Phosphodiesterase/genetics ; Sphingomyelin Phosphodiesterase/metabolism
Chemical Substances	Amitriptyline (1806D8D52K) ; Cholesterol (97C5T2UQ7J) ; N-Terminal Acetyltransferase A (EC 2.3.1.254) ; NAA10 protein, human (EC 2.3.1.255) ; Naa10 protein, mouse (EC 2.3.1.255) ; N-Terminal Acetyltransferase E (EC 2.3.1.258) ; ASMase, mouse (EC 3.1.4.12) ; SMPD1 protein, human (EC 3.1.4.12) ; Sphingomyelin Phosphodiesterase (EC 3.1.4.12)
Language	English
Publishing date	2013-05-23
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	605953-3
ISSN	1600-0641 ; 0168-8278
ISSN (online)	1600-0641
ISSN	0168-8278
DOI	10.1016/j.jhep.2013.05.023
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2027: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Bonn / Germany

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito