LIVIVO - Search results -

Search results

Result 1 - 10 of total 17

Search options

Article: The Exploitation of Lysosomes in Cancer Therapy with Graphene-Based Nanomaterials.

Ristic, Biljana / Bosnjak, Mihajlo / Misirkic Marjanovic, Maja / Stevanovic, Danijela / Janjetovic, Kristina / Harhaji-Trajkovic, Ljubica

Pharmaceutics

2023 Volume 15, Issue 7

Abstract: Graphene-based nanomaterials (GNMs), including graphene, graphene oxide, reduced graphene oxide, and graphene quantum dots, may have direct anticancer activity or be used as nanocarriers for antitumor drugs. GNMs usually enter tumor cells by endocytosis ... ...

Abstract	Graphene-based nanomaterials (GNMs), including graphene, graphene oxide, reduced graphene oxide, and graphene quantum dots, may have direct anticancer activity or be used as nanocarriers for antitumor drugs. GNMs usually enter tumor cells by endocytosis and can accumulate in lysosomes. This accumulation prevents drugs bound to GNMs from reaching their targets, suppressing their anticancer effects. A number of chemical modifications are made to GNMs to facilitate the separation of anticancer drugs from GNMs at low lysosomal pH and to enable the lysosomal escape of drugs. Lysosomal escape may be associated with oxidative stress, permeabilization of the unstable membrane of cancer cell lysosomes, release of lysosomal enzymes into the cytoplasm, and cell death. GNMs can prevent or stimulate tumor cell death by inducing protective autophagy or suppressing autolysosomal degradation, respectively. Furthermore, because GNMs prevent bound fluorescent agents from emitting light, their separation in lysosomes may enable tumor cell identification and therapy monitoring. In this review, we explain how the characteristics of the lysosomal microenvironment and the unique features of tumor cell lysosomes can be exploited for GNM-based cancer therapy.
Language	English
Publishing date	2023-06-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics15071846
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: Dual anticancer role of metformin: an old drug regulating AMPK dependent/independent pathways in metabolic, oncogenic/tumorsuppresing and immunity context.

Misirkic Marjanovic, Maja S / Vucicevic, Ljubica M / Despotovic, Ana R / Stamenkovic, Marina M / Janjetovic, Kristina D

American journal of cancer research

2021 Volume 11, Issue 11, Page(s) 5625–5643

Abstract: Metformin has been known to treat type 2 diabetes for decades and is widely prescribed antidiabetic drug. Recently, its anticancer potential has also been discovered. Moreover, metformin has low cost thus it has attained profound research interest. ... ...

Abstract	Metformin has been known to treat type 2 diabetes for decades and is widely prescribed antidiabetic drug. Recently, its anticancer potential has also been discovered. Moreover, metformin has low cost thus it has attained profound research interest. Comprehensing the complexity of the molecular regulatory networks in cancer provides a mode for advancement of research in cancer development and treatment. Metformin targets many pathways that play an important role in cancer cell survival outcome. Here, we described anticancer activity of metformin on the AMPK dependent/independent mechanisms regulating metabolism, oncogene/tumor suppressor signaling pathways together with the issue of clinical studies. We also provided brief overwiev about recently described metformin's role in cancer immunity. Insight in these complex molecular networks, will simplify application of metformin in clinical trials and contribute to improvement of anti-cancer therapy.
Language	English
Publishing date	2021-11-15
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2589522-9
ISSN	2156-6976
ISSN	2156-6976
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells

Mandic, Milos / Misirkic Marjanovic, Maja / Vucicevic, Ljubica / Jovanovic, Maja / Bosnjak, Mihajlo / Perovic, Vladimir / Ristic, Biljana / Ciric, Darko / Harhaji-Trajkovic, Ljubica / Trajkovic, Vladimir

Life sciences. 2022 May 15, v. 297

2022

Abstract: We investigated the mechanisms and the role of autophagy in the differentiation of HL-60 human acute myeloid leukemia cells induced by protein kinase C (PKC) activator phorbol myristate acetate (PMA). PMA-triggered differentiation of HL-60 cells into ... ...

Abstract	We investigated the mechanisms and the role of autophagy in the differentiation of HL-60 human acute myeloid leukemia cells induced by protein kinase C (PKC) activator phorbol myristate acetate (PMA). PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by cell-cycle arrest accompanied by elevated expression of macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by the increase in intracellular acidification, accumulation/punctuation of autophagosome marker LC3-II, and the increase in autophagic flux. PMA also increased nuclear translocation of autophagy transcription factors TFEB, FOXO1, and FOXO3, as well as the expression of several autophagy-related (ATG) genes in HL-60 cells. PMA failed to activate autophagy inducer AMP-activated protein kinase (AMPK) and inhibit autophagy suppressor mechanistic target of rapamycin complex 1 (mTORC1). On the other hand, it readily stimulated the phosphorylation of mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) via a protein kinase C-dependent mechanism. Pharmacological or genetic inhibition of ERK or JNK suppressed PMA-triggered nuclear translocation of TFEB and FOXO1/3, ATG expression, dissociation of pro-autophagic beclin-1 from its inhibitor BCL2, autophagy induction, and differentiation of HL-60 cells into macrophage-like cells. Pharmacological or genetic inhibition of autophagy also blocked PMA-induced macrophage differentiation of HL-60 cells. Therefore, MAP kinases ERK and JNK control PMA-induced macrophage differentiation of HL-60 leukemia cells through AMPK/mTORC1-independent, TFEB/FOXO-mediated transcriptional and beclin-1-dependent post-translational activation of autophagy.
Keywords	AMP-activated protein kinase ; acetates ; acidification ; autophagosomes ; autophagy ; cell cycle checkpoints ; dissociation ; humans ; interleukin-8 ; macrophages ; mitogen-activated protein kinase ; myeloid leukemia ; phosphorylation ; protein kinase C ; rapamycin ; transcription (genetics)
Language	English
Dates of publication	2022-0515
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2022.120481
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Bonn / Germany

Z 73/732: 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: Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19.

Paunovic, Verica / Vucicevic, Ljubica / Misirkic Marjanovic, Maja / Perovic, Vladimir / Ristic, Biljana / Bosnjak, Mihajlo / Mandic, Milos / Stevanovic, Danijela / Harhaji-Trajkovic, Ljubica / Lalosevic, Jovan / Nikolic, Milos / Bonaci-Nikolic, Branka / Trajkovic, Vladimir

Cells

2023 Volume 12, Issue 9

Abstract: As autophagy can promote or inhibit inflammation, we examined autophagy-inflammation interplay in COVID-19. Autophagy markers in the blood of 19 control subjects and 26 COVID-19 patients at hospital admission and one week later were measured by ELISA, ... ...

Abstract	As autophagy can promote or inhibit inflammation, we examined autophagy-inflammation interplay in COVID-19. Autophagy markers in the blood of 19 control subjects and 26 COVID-19 patients at hospital admission and one week later were measured by ELISA, while cytokine levels were examined by flow cytometric bead immunoassay. The antiviral IFN-α and proinflammatory TNF, IL-6, IL-8, IL-17, IL-33, and IFN-γ were elevated in COVID-19 patients at both time points, while IL-10 and IL-1β were increased at admission and one week later, respectively. Autophagy markers LC3 and ATG5 were unaltered in COVID-19. In contrast, the concentration of autophagic cargo receptor p62 was significantly lower and positively correlated with TNF, IL-10, IL-17, and IL-33 at hospital admission, returning to normal levels after one week. The expression of SARS-CoV-2 proteins NSP5 or ORF3a in THP-1 monocytes caused an autophagy-independent decrease or autophagy-inhibition-dependent increase, respectively, of intracellular/secreted p62, as confirmed by immunoblot/ELISA. This was associated with an NSP5-mediated decrease in TNF/IL-10 mRNA and an ORF3a-mediated increase in TNF/IL-1β/IL-6/IL-10/IL-33 mRNA levels. A genetic knockdown of p62 mimicked the immunosuppressive effect of NSP5, and a p62 increase in autophagy-deficient cells mirrored the immunostimulatory action of ORF3a. In conclusion, the proinflammatory autophagy receptor p62 is reduced inacute COVID-19, and the balance between autophagy-independent decrease and autophagy blockade-dependent increase of p62 levels could affect SARS-CoV-induced inflammation.
MeSH term(s)	Humans ; Autophagy ; COVID-19/pathology ; Inflammation/metabolism ; Interleukin-10/blood ; Interleukin-17/blood ; Interleukin-33/blood ; Interleukin-6/blood ; RNA, Messenger ; SARS-CoV-2
Chemical Substances	Interleukin-10 (130068-27-8) ; Interleukin-17 ; Interleukin-33 ; Interleukin-6 ; RNA, Messenger ; nuclear pore protein p62
Language	English
Publishing date	2023-04-28
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12091282
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Dual targeting of tumor cell energy metabolism and lysosomes as an anticancer strategy.

Paunovic, Verica / Kosic, Milica / Misirkic-Marjanovic, Maja / Trajkovic, Vladimir / Harhaji-Trajkovic, Ljubica

Biochimica et biophysica acta. Molecular cell research

2020 Volume 1868, Issue 4, Page(s) 118944

Abstract: To sustain their proliferative and metastatic capacity, tumor cells increase the activity of energy-producing pathways and lysosomal compartment, resorting to autophagolysosomal degradation when nutrients are scarce. Consequently, large fragile lysosomes ...

Abstract	To sustain their proliferative and metastatic capacity, tumor cells increase the activity of energy-producing pathways and lysosomal compartment, resorting to autophagolysosomal degradation when nutrients are scarce. Consequently, large fragile lysosomes and enhanced energy metabolism may serve as targets for anticancer therapy. A simultaneous induction of energy stress (by caloric restriction and inhibition of glycolysis, oxidative phosphorylation, Krebs cycle, or amino acid/fatty acid metabolism) and lysosomal stress (by lysosomotropic detergents, vacuolar ATPase inhibitors, or cationic amphiphilic drugs) is an efficient anti-cancer strategy demonstrated in a number of studies. However, the mechanisms of lysosomal/energy stress co-amplification, apart from the protective autophagy inhibition, are poorly understood. We here summarize the established and suggest potential mechanisms and candidates for anticancer therapy based on the dual targeting of lysosomes and energy metabolism.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Autophagy ; Energy Metabolism/drug effects ; Humans ; Lysosomes/drug effects ; Lysosomes/metabolism ; Neoplasms/drug therapy ; Neoplasms/metabolism
Language	English
Publishing date	2020-12-28
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbamcr.2020.118944
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

Uc I Zs.247: 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 ▾

Article ; Online: MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells.

Life sciences

2022 Volume 297, Page(s) 120481

Abstract	We investigated the mechanisms and the role of autophagy in the differentiation of HL-60 human acute myeloid leukemia cells induced by protein kinase C (PKC) activator phorbol myristate acetate (PMA). PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by cell-cycle arrest accompanied by elevated expression of macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by the increase in intracellular acidification, accumulation/punctuation of autophagosome marker LC3-II, and the increase in autophagic flux. PMA also increased nuclear translocation of autophagy transcription factors TFEB, FOXO1, and FOXO3, as well as the expression of several autophagy-related (ATG) genes in HL-60 cells. PMA failed to activate autophagy inducer AMP-activated protein kinase (AMPK) and inhibit autophagy suppressor mechanistic target of rapamycin complex 1 (mTORC1). On the other hand, it readily stimulated the phosphorylation of mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) via a protein kinase C-dependent mechanism. Pharmacological or genetic inhibition of ERK or JNK suppressed PMA-triggered nuclear translocation of TFEB and FOXO1/3, ATG expression, dissociation of pro-autophagic beclin-1 from its inhibitor BCL2, autophagy induction, and differentiation of HL-60 cells into macrophage-like cells. Pharmacological or genetic inhibition of autophagy also blocked PMA-induced macrophage differentiation of HL-60 cells. Therefore, MAP kinases ERK and JNK control PMA-induced macrophage differentiation of HL-60 leukemia cells through AMPK/mTORC1-independent, TFEB/FOXO-mediated transcriptional and beclin-1-dependent post-translational activation of autophagy.
MeSH term(s)	Autophagy ; Extracellular Signal-Regulated MAP Kinases/metabolism ; HL-60 Cells ; Humans ; Leukemia ; Macrophages/metabolism ; Tetradecanoylphorbol Acetate/metabolism ; Tetradecanoylphorbol Acetate/pharmacology
Chemical Substances	Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24) ; Tetradecanoylphorbol Acetate (NI40JAQ945)
Language	English
Publishing date	2022-03-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2022.120481
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.368: 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: Mechanisms and therapeutic significance of autophagy modulation by antipsychotic drugs.

Vucicevic, Ljubica / Misirkic-Marjanovic, Maja / Harhaji-Trajkovic, Ljubica / Maric, Nadja / Trajkovic, Vladimir

Cell stress

2018 Volume 2, Issue 11, Page(s) 282–291

Abstract: In this review we analyze the ability of antipsychotic medications to modulate macroautophagy, a process of controlled lysosomal digestion of cellular macromolecules and organelles. We focus on its molecular mechanisms, consequences for the function/ ... ...

Abstract	In this review we analyze the ability of antipsychotic medications to modulate macroautophagy, a process of controlled lysosomal digestion of cellular macromolecules and organelles. We focus on its molecular mechanisms, consequences for the function/survival of neuronal and other cells, and the contribution to the beneficial and side-effects of antipsychotics in the treatment of schizophrenia, neurodegeneration, and cancer. A wide range of antipsychotics was able to induce neuronal autophagy as a part of the adaptive stress response apparently independent of mammalian target of rapamycin and dopamine receptor blockade. Autophagy induction by antipsychotics could contribute to reducing neuronal dysfunction in schizophrenia, but also to the adverse effects associated with their long-term use, such as brain volume loss and weight gain. In neurodegenerative diseases, antipsychotic-stimulated autophagy might help to increase the clearance and reduce neurotoxicity of aggregated proteotoxins. However, the possibility that some antipsychotics might block autophagic flux and potentially contribute to proteotoxin-mediated neurodegeneration must be considered. Finally, the anticancer effects of autophagy induction by antipsychotics make plausible their repurposing as adjuncts to standard cancer therapy.
Language	English
Publishing date	2018-10-25
Publishing country	Austria
Document type	Journal Article ; Review
ISSN	2523-0204
ISSN (online)	2523-0204
DOI	10.15698/cst2018.11.161
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: Mesenchymal Stem Cells Promote Metastasis of Lung Cancer Cells by Downregulating Systemic Antitumor Immune Response.

Gazdic, Marina / Simovic Markovic, Bojana / Jovicic, Nemanja / Misirkic-Marjanovic, Maja / Djonov, Valentin / Jakovljevic, Vladimir / Arsenijevic, Nebojsa / Lukic, Miodrag L / Volarevic, Vladislav

Stem cells international

2017 Volume 2017, Page(s) 6294717

Abstract: Since majority of systemically administered mesenchymal stem cells (MSCs) become entrapped within the lungs, we used metastatic model of lung cancer, induced by intravenous injection of Lewis lung cancer 1 (LLC1) cells, to investigate the molecular ... ...

Abstract	Since majority of systemically administered mesenchymal stem cells (MSCs) become entrapped within the lungs, we used metastatic model of lung cancer, induced by intravenous injection of Lewis lung cancer 1 (LLC1) cells, to investigate the molecular mechanisms involved in MSC-mediated modulation of metastasis. MSCs significantly augmented lung cancer metastasis, attenuate concentrations of proinflammatory cytokines (TNF-
Language	English
Publishing date	2017-07-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2573856-2
ISSN	1687-9678 ; 1687-966X
ISSN (online)	1687-9678
ISSN	1687-966X
DOI	10.1155/2017/6294717
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Coordinated activation of AMP-activated protein kinase, extracellular signal-regulated kinase, and autophagy regulates phorbol myristate acetate-induced differentiation of SH-SY5Y neuroblastoma cells.

Zogovic, Nevena / Tovilovic-Kovacevic, Gordana / Misirkic-Marjanovic, Maja / Vucicevic, Ljubica / Janjetovic, Kristina / Harhaji-Trajkovic, Ljubica / Trajkovic, Vladimir

Journal of neurochemistry

2014 Volume 133, Issue 2, Page(s) 223–232

Abstract: We explored the interplay between the intracellular energy sensor AMP-activated protein kinase (AMPK), extracellular signal-regulated kinase (ERK), and autophagy in phorbol myristate acetate (PMA)-induced neuronal differentiation of SH-SY5Y human ... ...

Abstract	We explored the interplay between the intracellular energy sensor AMP-activated protein kinase (AMPK), extracellular signal-regulated kinase (ERK), and autophagy in phorbol myristate acetate (PMA)-induced neuronal differentiation of SH-SY5Y human neuroblastoma cells. PMA-triggered expression of neuronal markers (dopamine transporter, microtubule-associated protein 2, β-tubulin) was associated with an autophagic response, measured by the conversion of microtubule-associated protein light chain 3 (LC3)-I to autophagosome-bound LC3-II, increase in autophagic flux, and expression of autophagy-related (Atg) proteins Atg7 and beclin-1. This coincided with the transient activation of AMPK and sustained activation of ERK. Pharmacological inhibition or RNA interference-mediated silencing of AMPK suppressed PMA-induced expression of neuronal markers, as well as ERK activation and autophagy. A selective pharmacological blockade of ERK prevented PMA-induced neuronal differentiation and autophagy induction without affecting AMPK phosphorylation. Conversely, the inhibition of autophagy downstream of AMPK/ERK, either by pharmacological agents or LC3 knockdown, promoted the expression of neuronal markers, thus indicating a role of autophagy in the suppression of PMA-induced differentiation of SH-SY5Y cells. Therefore, PMA-induced neuronal differentiation of SH-SY5Y cells depends on a complex interplay between AMPK, ERK, and autophagy, in which the stimulatory effects of AMPK/ERK signaling are counteracted by the coinciding autophagic response. Phorbol myristate acetate (PMA) induces the expression of dopamine transporter, microtubule-associated protein 2, and β-tubulin, and subsequent neuronal differentiation of SH-SY5Y neuroblastoma cells through AMP-activated protein kinase (AMPK)-dependent activation of extracellular signal-regulated kinase (ERK). The activation of AMPK/ERK axis also induces the expression of beclin-1 and Atg7, and increases LC3 conversion, thereby triggering the autophagic response that counteracts differentiation process.
MeSH term(s)	AMP-Activated Protein Kinases/metabolism ; Autophagy/drug effects ; Autophagy-Related Protein 7 ; Autophagy-Related Protein-1 Homolog ; Cell Differentiation/drug effects ; Cell Line, Tumor ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Enzyme Activation/drug effects ; Enzyme Inhibitors/pharmacology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Gene Expression Regulation, Enzymologic/drug effects ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Microtubule-Associated Proteins/metabolism ; Neuroblastoma/pathology ; Protein Serine-Threonine Kinases/metabolism ; RNA Interference/physiology ; Tetradecanoylphorbol Acetate/pharmacology ; Ubiquitin-Activating Enzymes/metabolism
Chemical Substances	Dopamine Plasma Membrane Transport Proteins ; Enzyme Inhibitors ; Intracellular Signaling Peptides and Proteins ; MAP1LC3A protein, human ; MAP2 protein, human ; Microtubule-Associated Proteins ; Autophagy-Related Protein-1 Homolog (EC 2.7.11.1) ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; ULK1 protein, human (EC 2.7.11.1) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24) ; AMP-Activated Protein Kinases (EC 2.7.11.31) ; ATG7 protein, human (EC 6.2.1.45) ; Autophagy-Related Protein 7 (EC 6.2.1.45) ; Ubiquitin-Activating Enzymes (EC 6.2.1.45) ; Tetradecanoylphorbol Acetate (NI40JAQ945)
Language	English
Publishing date	2014-11-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1111/jnc.12980
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ui II Zs.170: 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: Autophagy inhibition uncovers the neurotoxic action of the antipsychotic drug olanzapine.

Vucicevic, Ljubica / Misirkic-Marjanovic, Maja / Paunovic, Verica / Kravic-Stevovic, Tamara / Martinovic, Tamara / Ciric, Darko / Maric, Nadja / Petricevic, Sasa / Harhaji-Trajkovic, Ljubica / Bumbasirevic, Vladimir / Trajkovic, Vladimir

Autophagy

2014 Volume 10, Issue 12, Page(s) 2362–2378

Abstract: We investigated the role of autophagy, a controlled cellular self-digestion process, in regulating survival of neurons exposed to atypical antipsychotic olanzapine. Olanzapine induced autophagy in human SH-SY5Y neuronal cell line, as confirmed by the ... ...

Abstract	We investigated the role of autophagy, a controlled cellular self-digestion process, in regulating survival of neurons exposed to atypical antipsychotic olanzapine. Olanzapine induced autophagy in human SH-SY5Y neuronal cell line, as confirmed by the increase in autophagic flux and presence of autophagic vesicles, fusion of autophagosomes with lysosomes, and increase in the expression of autophagy-related (ATG) genes ATG4B, ATG5, and ATG7. The production of reactive oxygen species, but not modulation of the main autophagy repressor MTOR or its upstream regulators AMP-activated protein kinase and AKT1, was responsible for olanzapine-triggered autophagy. Olanzapine-mediated oxidative stress also induced mitochondrial depolarization and damage, and the autophagic clearance of dysfunctional mitochondria was confirmed by electron microscopy, colocalization of autophagosome-associated MAP1LC3B (LC3B henceforth) and mitochondria, and mitochondrial association with the autophagic cargo receptor SQSTM1/p62. While olanzapine-triggered mitochondrial damage was not overtly toxic to SH-SY5Y cells, their death was readily initiated upon the inhibition of autophagy with pharmacological inhibitors, RNA interference knockdown of BECN1 and LC3B, or biological free radical nitric oxide. The treatment of mice with olanzapine for 14 d increased the brain levels of autophagosome-associated LC3B-II and mRNA encoding Atg4b, Atg5, Atg7, Atg12, Gabarap, and Becn1. The administration of the autophagy inhibitor chloroquine significantly increased the expression of proapoptotic genes (Trp53, Bax, Bak1, Pmaip1, Bcl2l11, Cdkn1a, and Cdkn1b) and DNA fragmentation in the frontal brain region of olanzapine-exposed animals. These data indicate that olanzapine-triggered autophagy protects neurons from otherwise fatal mitochondrial damage, and that inhibition of autophagy might unmask the neurotoxic action of the drug.
MeSH term(s)	AMP-Activated Protein Kinases/metabolism ; Animals ; Antipsychotic Agents/pharmacology ; Apoptosis/drug effects ; Autophagy/drug effects ; Benzodiazepines/pharmacology ; Cell Line ; Humans ; Lysosomes/drug effects ; Mice ; Mitochondria/drug effects ; Neurons/cytology ; Neurons/drug effects ; Reactive Oxygen Species/metabolism
Chemical Substances	Antipsychotic Agents ; Reactive Oxygen Species ; Benzodiazepines (12794-10-4) ; AMP-Activated Protein Kinases (EC 2.7.11.31) ; olanzapine (N7U69T4SZR)
Language	English
Publishing date	2014
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2454135-7
ISSN	1554-8635 ; 1554-8627
ISSN (online)	1554-8635
ISSN	1554-8627
DOI	10.4161/15548627.2014.984270
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 6741: 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 ▾

To top

More links

Kategorien

Order via subito

More links

Kategorien

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

Full text online

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

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

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito