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  1. Article ; Online: The yeast mitochondrial proteins Rcf1 and Rcf2 support the enzymology of the cytochrome

    Strogolova, Vera / Hoang, Ngoc H / Hosler, Jonathan / Stuart, Rosemary A

    The Journal of biological chemistry

    2019  Volume 294, Issue 13, Page(s) 4867–4877

    Abstract: The yeast mitochondrial proteins Rcf1 and Rcf2 are associated with a subpopulation of the ... ...

    Abstract The yeast mitochondrial proteins Rcf1 and Rcf2 are associated with a subpopulation of the cytochrome
    MeSH term(s) Electron Transport Complex IV/genetics ; Electron Transport Complex IV/metabolism ; Mutation ; Oxygen Consumption/physiology ; Proton-Motive Force/physiology ; Saccharomyces cerevisiae/enzymology ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism
    Chemical Substances Rcf1 protein, S cerevisiae ; Saccharomyces cerevisiae Proteins ; Electron Transport Complex IV (EC 1.9.3.1)
    Language English
    Publishing date 2019-01-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.RA118.006888
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.108: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Increased platelet mitochondrial function correlates with clot strength in a rodent fracture model.

    Littlejohn, James Blake / Grenn, Emily Evans / Carter, Kristen T / Palei, Ana C / Spradley, Frank T / Hosler, Jonathan P / Hoang, Ngoc H / Edwards, Kristin S / Kutcher, Matthew E

    The journal of trauma and acute care surgery

    2023  Volume 96, Issue 3, Page(s) 378–385

    Abstract: Background: Thromboelastographic measures of clot strength increase early after injury, portending higher risks for thromboembolic complications during recovery. Understanding the specific role of platelets is challenging because of a lack of clinically ...

    Abstract Background: Thromboelastographic measures of clot strength increase early after injury, portending higher risks for thromboembolic complications during recovery. Understanding the specific role of platelets is challenging because of a lack of clinically relevant measures of platelet function. Platelet mitochondrial respirometry may provide insight to global platelet function but has not yet been correlated with functional coagulation studies.
    Methods: Wistar rats underwent anesthesia and either immediate sacrifice for baseline values (n = 6) or (1) bilateral hindlimb orthopedic injury (n = 12), versus (2) sham anesthesia (n = 12) with terminal phlebotomy/hepatectomy after 24 hours. High-resolution respirometry was used to measure basal respiration, mitochondrial leak, maximal oxidative phosphorylation, and Complex IV activity in intact platelets; Complex I- and Complex II-driven respiration was measured in isolated liver mitochondria. Results were normalized to platelet number and protein mass, respectively. Citrated native thromboelastography (TEG) was performed in triplicate.
    Results: Citrated native TEG maximal amplitude was significantly higher (81.0 ± 3.0 vs. 73.3 ± 3.5 mm, p < 0.001) in trauma compared with sham rats 24 hours after injury. Intact platelets from injured rats had higher basal oxygen consumption (17.7 ± 2.5 vs. 15.1 ± 3.2 pmol O 2 /[s × 10 8 cells], p = 0.045), with similar trends in mitochondrial leak rate ( p = 0.19) when compared with sham animals. Overall, platelet basal respiration significantly correlated with TEG maximal amplitude ( r = 0.44, p = 0.034). As a control for sex-dependent systemic mitochondrial differences, females displayed higher liver mitochondria Complex I-driven respiration (895.6 ± 123.7 vs. 622.1 ± 48.7 mmol e - /min/mg protein, p = 0.02); as a control for systemic mitochondrial effects of injury, no liver mitochondrial respiration differences were seen.
    Conclusion: Platelet mitochondrial basal respiration is increased after injury and correlates with clot strength in this rodent hindlimb fracture model. Several mitochondrial-targeted therapeutics exist in common use that are underexplored but hold promise as potential antithrombotic adjuncts that can be sensitively evaluated in this preclinical model.
    MeSH term(s) Female ; Animals ; Rats ; Rodentia ; Rats, Wistar ; Mitochondria/metabolism ; Blood Platelets/metabolism ; Hemostasis ; Thrombelastography/methods ; Fractures, Bone
    Language English
    Publishing date 2023-09-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2651070-4
    ISSN 2163-0763 ; 2163-0755
    ISSN (online) 2163-0763
    ISSN 2163-0755
    DOI 10.1097/TA.0000000000004204
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 127: 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)

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  3. Article ; Online: Hypoxia-inducible gene domain 1 proteins in yeast mitochondria protect against proton leak through complex IV.

    Hoang, Ngoc H / Strogolova, Vera / Mosley, Jaramys J / Stuart, Rosemary A / Hosler, Jonathan

    The Journal of biological chemistry

    2019  Volume 294, Issue 46, Page(s) 17669–17677

    Abstract: Hypoxia-inducible gene domain 1 (HIGD1) proteins are small integral membrane proteins, conserved from bacteria to humans, that associate with oxidative phosphorylation supercomplexes. Using yeast as a model organism, we have shown previously that its two ...

    Abstract Hypoxia-inducible gene domain 1 (HIGD1) proteins are small integral membrane proteins, conserved from bacteria to humans, that associate with oxidative phosphorylation supercomplexes. Using yeast as a model organism, we have shown previously that its two HIGD1 proteins, Rcf1 and Rcf2, are required for the generation and maintenance of a normal membrane potential (ΔΨ) across the inner mitochondrial membrane (IMM). We postulated that the lower ΔΨ observed in the absence of the HIGD1 proteins may be due to decreased proton pumping by complex IV (CIV) or enhanced leak of protons across the IMM. Here we measured the ΔΨ generated by complex III (CIII) to discriminate between these possibilities. First, we found that the decreased ΔΨ observed in the absence of the HIGD1 proteins cannot be due to decreased proton pumping by CIV because CIII, operating alone, also exhibited a decreased ΔΨ when HIGD1 proteins were absent. Because CIII can neither lower its pumping stoichiometry nor transfer protons completely across the IMM, this result indicates that HIGD1 protein ablation enhances proton leak across the IMM. Second, we demonstrate that this proton leak occurs through CIV because ΔΨ generation by CIII is restored when CIV is removed from the cell. Third, the proton leak appeared to take place through an inactive population of CIV that accumulates when HIGD1 proteins are absent. We conclude that HIGD1 proteins in yeast prevent CIV inactivation, likely by preventing the loss of lipids bound within the Cox3 protein of CIV.
    MeSH term(s) Electron Transport Complex IV/chemistry ; Electron Transport Complex IV/genetics ; Humans ; Membrane Potentials/genetics ; Mitochondrial Membranes/chemistry ; Oxidative Phosphorylation ; Protective Agents/chemistry ; Proton Pumps/chemistry ; Protons ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/chemistry ; Saccharomyces cerevisiae Proteins/genetics
    Chemical Substances Protective Agents ; Proton Pumps ; Protons ; Rcf1 protein, S cerevisiae ; Rcf2 protein, S cerevisiae ; Saccharomyces cerevisiae Proteins ; COX3 protein, S cerevisiae (EC 1.9.3.1) ; Electron Transport Complex IV (EC 1.9.3.1)
    Language English
    Publishing date 2019-10-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.RA119.010317
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.108: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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  4. Article ; Online: Mitochondrial function and oxidative stress in white adipose tissue in a rat model of PCOS: effect of SGLT2 inhibition.

    Pruett, Jacob E / Everman, Steven J / Hoang, Ngoc H / Salau, Faridah / Taylor, Lucy C / Edwards, Kristin S / Hosler, Jonathan P / Huffman, Alexandra M / Romero, Damian G / Yanes Cardozo, Licy L

    Biology of sex differences

    2022  Volume 13, Issue 1, Page(s) 45

    Abstract: Background: Polycystic ovary syndrome (PCOS), characterized by androgen excess and ovulatory dysfunction, is associated with a high prevalence of obesity and insulin resistance (IR) in women. We demonstrated that sodium-glucose cotransporter-2 inhibitor ...

    Abstract Background: Polycystic ovary syndrome (PCOS), characterized by androgen excess and ovulatory dysfunction, is associated with a high prevalence of obesity and insulin resistance (IR) in women. We demonstrated that sodium-glucose cotransporter-2 inhibitor (SGLT2i) administration decreases fat mass without affecting IR in the PCOS model. In male models of IR, administration of SGLT2i decreases oxidative stress and improves mitochondrial function in white adipose tissue (WAT). Therefore, we hypothesized that SGLT2i reduces adiposity via improvement in mitochondrial function and oxidative stress in WAT in PCOS model.
    Methods: Four-week-old female rats were treated with dihydrotestosterone for 90 days (PCOS model), and SGLT2i (empagliflozin) was co-administered during the last 3 weeks. Body composition was measured before and after SGLT2i treatment by EchoMRI. Subcutaneous (SAT) and visceral (VAT) WAT were collected for histological and molecular studies at the end of the study.
    Results: PCOS model had an increase in food intake, body weight, body mass index, and fat mass/lean mass ratio compared to the control group. SGLT2i lowered fat mass/lean ratio in PCOS. Glucosuria was observed in both groups, but had a larger magnitude in controls. The net glucose balance was similar in both SGLT2i-treated groups. The PCOS SAT had a higher frequency of small adipocytes and a lower frequency of large adipocytes. In SAT of controls, SGLT2i increased frequencies of small and medium adipocytes while decreasing the frequency of large adipocytes, and this effect was blunted in PCOS. In VAT, PCOS had a lower frequency of small adipocytes while SGLT2i increased the frequency of small adipocytes in PCOS. PCOS model had decreased mitochondrial content in SAT and VAT without impacting oxidative stress in WAT or the circulation. SGLT2i did not modify mitochondrial function or oxidative stress in WAT in both treated groups.
    Conclusions: Hyperandrogenemia in PCOS causes expansion of WAT, which is associated with decreases in mitochondrial content and function in SAT and VAT. SGLT2i increases the frequency of small adipocytes in VAT only without affecting mitochondrial dysfunction, oxidative stress, or IR in the PCOS model. SGLT2i decreases adiposity independently of adipose mitochondrial and oxidative stress mechanisms in the PCOS model.
    MeSH term(s) Adipose Tissue, White ; Animals ; Diabetes Mellitus, Type 2 ; Female ; Glucose ; Humans ; Insulin Resistance/physiology ; Male ; Mitochondria ; Obesity ; Oxidative Stress ; Polycystic Ovary Syndrome/drug therapy ; Rats ; Sodium-Glucose Transporter 2 ; Sodium-Glucose Transporter 2 Inhibitors/pharmacology
    Chemical Substances Sodium-Glucose Transporter 2 ; Sodium-Glucose Transporter 2 Inhibitors ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2022-08-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2587352-0
    ISSN 2042-6410 ; 2042-6410
    ISSN (online) 2042-6410
    ISSN 2042-6410
    DOI 10.1186/s13293-022-00455-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Angiotensin II type 1 receptor agonistic autoantibody blockade improves postpartum hypertension and cardiac mitochondrial function in rat model of preeclampsia.

    Booz, George W / Kennedy, Daniel / Bowling, Michael / Robinson, Taprieka / Azubuike, Daniel / Fisher, Brandon / Brooks, Karen / Chinthakuntla, Pooja / Hoang, Ngoc H / Hosler, Jonathan P / Cunningham, Mark W

    Biology of sex differences

    2021  Volume 12, Issue 1, Page(s) 58

    Abstract: Women with preeclampsia (PE) have a greater risk of developing hypertension, cardiovascular disease (CVD), and renal disease later in life. Angiotensin II type I receptor agonistic autoantibodies (AT1-AAs) are elevated in women with PE during pregnancy ... ...

    Abstract Women with preeclampsia (PE) have a greater risk of developing hypertension, cardiovascular disease (CVD), and renal disease later in life. Angiotensin II type I receptor agonistic autoantibodies (AT1-AAs) are elevated in women with PE during pregnancy and up to 2-year postpartum (PP), and in the reduced uterine perfusion pressure (RUPP) rat model of PE. Blockade of AT1-AA with a specific 7 amino acid peptide binding sequence ('n7AAc') improves pathophysiology observed in RUPP rats; however, the long-term effects of AT1-AA inhibition in PP is unknown. Pregnant Sprague Dawley rats were divided into three groups: normal pregnant (NP) (n = 16), RUPP (n = 15), and RUPP + 'n7AAc' (n = 16). Gestational day 14, RUPP surgery was performed and 'n7AAc' (144 μg/day) administered via osmotic minipump. At 10-week PP, mean arterial pressure (MAP), renal glomerular filtration rate (GFR) and cardiac functions, and cardiac mitochondria function were assessed. MAP was elevated PP in RUPP vs. NP (126 ± 4 vs. 116 ± 3 mmHg, p < 0.05), but was normalized in in RUPP + 'n7AAc' (109 ± 3 mmHg) vs. RUPP (p < 0.05). PP heart size was reduced by RUPP + 'n7AAc' vs. RUPP rats (p < 0.05). Complex IV protein abundance and enzymatic activity, along with glutamate/malate-driven respiration (complexes I, III, and IV), were reduced in the heart of RUPP vs. NP rats which was prevented with 'n7AAc'. AT1-AA inhibition during pregnancy not only improves blood pressure and pathophysiology of PE in rats during pregnancy, but also long-term changes in blood pressure, cardiac hypertrophy, and cardiac mitochondrial function PP.
    MeSH term(s) Angiotensin II Type 1 Receptor Blockers/pharmacology ; Animals ; Autoantibodies/pharmacology ; Female ; Hypertension/drug therapy ; Mitochondria, Heart/physiology ; Placenta ; Postpartum Period ; Pre-Eclampsia/drug therapy ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Receptor, Angiotensin, Type 1
    Chemical Substances Angiotensin II Type 1 Receptor Blockers ; Autoantibodies ; Receptor, Angiotensin, Type 1
    Language English
    Publishing date 2021-11-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2587352-0
    ISSN 2042-6410 ; 2042-6410
    ISSN (online) 2042-6410
    ISSN 2042-6410
    DOI 10.1186/s13293-021-00396-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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