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[PMID]:28493473
[Au] Autor:Tahrir FG; Shanmughapriya S; Ahooyi TM; Knezevic T; Gupta MK; Kontos CD; McClung JM; Madesh M; Gordon J; Feldman AM; Cheung JY; Khalili K
[Ad] Endereço:Department of Neuroscience, Center for Neurovirology, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.
[Ti] Título:Dysregulation of mitochondrial bioenergetics and quality control by HIV-1 Tat in cardiomyocytes.
[So] Source:J Cell Physiol;233(2):748-758, 2018 Feb.
[Is] ISSN:1097-4652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cardiovascular disease remains a leading cause of morbidity and mortality in HIV-positive patients, even in those whose viral loads are well controlled with antiretroviral therapy. However, the underlying molecular events responsible for the development of cardiac disease in the setting of HIV remain unknown. The HIV-encoded Tat protein plays a critical role in the activation of HIV gene expression and profoundly impacts homeostasis in both HIV-infected cells and uninfected cells that have taken up released Tat via a bystander effect. Since cardiomyocyte function, including excitation-contraction coupling, greatly depends on energy provided by the mitochondria, in this study, we performed a series of experiments to assess the impact of Tat on mitochondrial function and bioenergetics pathways in a primary cell culture model derived from neonatal rat ventricular cardiomyocytes (NRVCs). Our results show that the presence of Tat in cardiomyocytes is accompanied by a decrease in oxidative phosphorylation, a decline in the levels of ATP, and an accumulation of reactive oxygen species (ROS). Tat impairs the uptake of mitochondrial Ca ([Ca ] ) and the electrophysiological activity of cardiomyocytes. Tat also affects the protein clearance pathway and autophagy in cardiomyocytes under stress due to hypoxia-reoxygenation conditions. A reduction in the level of ubiquitin along with dysregulated degradation of autophagy proteins including SQSTM1/p62 and a reduction of LC3 II were detected in cardiomyocytes harboring Tat. These results suggest that, by targeting mitochondria and protein quality control, Tat significantly impacts bioenergetics and autophagy resulting in dysregulation of cardiomyocyte health and homeostasis.
[Mh] Termos MeSH primário: Metabolismo Energético
HIV-1/metabolismo
Mitocôndrias Cardíacas/metabolismo
Miócitos Cardíacos/metabolismo
Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismo
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/metabolismo
Animais
Apoptose
Autofagia
Cálcio/metabolismo
Canais de Cálcio/metabolismo
Hipóxia Celular
Células Cultivadas
Interações Hospedeiro-Patógeno
Potenciais da Membrana
Proteínas Associadas aos Microtúbulos/metabolismo
Mitocôndrias Cardíacas/virologia
Degradação Mitocondrial
Miócitos Cardíacos/virologia
Fosforilação Oxidativa
Cultura Primária de Células
Ratos Sprague-Dawley
Espécies Reativas de Oxigênio/metabolismo
Proteína Sequestossoma-1/metabolismo
Transdução de Sinais
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channels); 0 (LC3 protein, rat); 0 (Microtubule-Associated Proteins); 0 (Reactive Oxygen Species); 0 (Sequestosome-1 Protein); 0 (Sqstm1 protein, rat); 0 (mitochondrial calcium uniporter); 0 (tat Gene Products, Human Immunodeficiency Virus); 8L70Q75FXE (Adenosine Triphosphate); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170512
[St] Status:MEDLINE
[do] DOI:10.1002/jcp.26002


  2 / 11329 MEDLINE  
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[PMID]:29217757
[Au] Autor:Daubert MA; Yow E; Dunn G; Marchev S; Barnhart H; Douglas PS; O'Connor C; Goldstein S; Udelson JE; Sabbah HN
[Ad] Endereço:From the Duke University Medical Center, Duke Clinical Research Institute, Durham, NC (M.A.D., E.Y., G.D., H.B., P.S.D.); Medical University of Pleven, Bulgaria (S.M.); Inova Heart and Vascular Institute, Falls Church, VA (C.O.); Henry Ford Hospital, Detroit, MI (S.G., H.N.S.); and Tufts Medical Cen
[Ti] Título:Novel Mitochondria-Targeting Peptide in Heart Failure Treatment: A Randomized, Placebo-Controlled Trial of Elamipretide.
[So] Source:Circ Heart Fail;10(12), 2017 Dec.
[Is] ISSN:1941-3297
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Mitochondrial dysfunction and energy depletion in the failing heart are innovative therapeutic targets in heart failure management. Elamipretide is a novel tetrapeptide that increases mitochondrial energy; however, its safety, tolerability, and therapeutic effect on cardiac structure and function have not been studied in heart failure with reduced ejection fraction. METHODS AND RESULTS: In this double-blind, placebo-controlled, ascending-dose trial, patients with heart failure with reduced ejection fraction (ejection fraction, ≤35%) were randomized to either a single 4-hour infusion of elamipretide (cohort 1 [n=8], 0.005; cohort 2 [n=8], 0.05; and cohort 3 [n=8], 0.25 mg·kg ·h ) or placebo control (n=12). Safety and efficacy were assessed by clinical, laboratory, and echocardiographic assessments performed at pre-, mid- and end-infusion and 6-, 8-, 12- and 24-hours postinfusion start. Peak plasma concentrations of elamipretide occurred at end-infusion and were undetectable by 24 hours postinfusion. There were no serious adverse events. Blood pressure and heart rate remained stable in all cohorts. Compared with placebo, a significant decrease in left ventricular end-diastolic volume (-18 mL; =0.009) and end-systolic volume (-14 mL; =0.005) occurred at end infusion in the highest dose cohort. CONCLUSIONS: This is the first study to evaluate elamipretide in heart failure with reduced ejection fraction and demonstrates that a single infusion of elamipretide is safe and well tolerated. High-dose elamipretide resulted in favorable changes in left ventricular volumes that correlated with peak plasma concentrations, supporting a temporal association and dose-effect relationship. Further study of elamipretide is needed to determine long-term safety and efficacy. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02388464.
[Mh] Termos MeSH primário: Fármacos Cardiovasculares/administração & dosagem
Metabolismo Energético/efeitos dos fármacos
Insuficiência Cardíaca/tratamento farmacológico
Mitocôndrias Cardíacas/efeitos dos fármacos
Oligopeptídeos/administração & dosagem
[Mh] Termos MeSH secundário: Idoso
Bulgária
Fármacos Cardiovasculares/efeitos adversos
Fármacos Cardiovasculares/sangue
Fármacos Cardiovasculares/farmacocinética
Método Duplo-Cego
Ecocardiografia
Feminino
Insuficiência Cardíaca/diagnóstico
Insuficiência Cardíaca/metabolismo
Insuficiência Cardíaca/fisiopatologia
Seres Humanos
Infusões Intravenosas
Masculino
Meia-Idade
Mitocôndrias Cardíacas/metabolismo
Oligopeptídeos/efeitos adversos
Oligopeptídeos/sangue
Oligopeptídeos/farmacocinética
Estudos Prospectivos
Volume Sistólico/efeitos dos fármacos
Resultado do Tratamento
Função Ventricular Esquerda/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Cardiovascular Agents); 0 (Oligopeptides); 0 (arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180207
[Lr] Data última revisão:
180207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE


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[PMID]:28450394
[Au] Autor:Korge P; John SA; Calmettes G; Weiss JN
[Ad] Endereço:From the UCLA Cardiovascular Research Laboratory and the Departments of Medicine (Cardiology) and Physiology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095.
[Ti] Título:Reactive oxygen species production induced by pore opening in cardiac mitochondria: The role of complex II.
[So] Source:J Biol Chem;292(24):9896-9905, 2017 06 16.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Succinate-driven reverse electron transport (RET) through complex I is hypothesized to be a major source of reactive oxygen species (ROS) that induces permeability transition pore (PTP) opening and damages the heart during ischemia/reperfusion. Because RET can only generate ROS when mitochondria are fully polarized, this mechanism is self-limiting once PTP opens during reperfusion. In the accompanying article (Korge, P., Calmettes, G., John, S. A., and Weiss, J. N. (2017) 292, 9882-9895), we showed that ROS production after PTP opening can be sustained when complex III is damaged (simulated by antimycin). Here we show that complex II can also contribute to sustained ROS production in isolated rabbit cardiac mitochondria following inner membrane pore formation induced by either alamethicin or calcium-induced PTP opening. Two conditions are required to maximize malonate-sensitive ROS production by complex II in isolated mitochondria: ( ) complex II inhibition by atpenin A5 or complex III inhibition by stigmatellin that results in succinate-dependent reduction of the dicarboxylate-binding site of complex II (site II ); ( ) pore opening in the inner membrane resulting in rapid efflux of succinate/fumarate and other dicarboxylates capable of competitively binding to site II The decrease in matrix [dicarboxylate] allows O access to reduced site II , thereby making electron donation to O possible, explaining the rapid increase in ROS production provided that site II is reduced. Because ischemia is known to inhibit complexes II and III and increase matrix succinate/fumarate levels, we hypothesize that by allowing dicarboxylate efflux from the matrix, PTP opening during reperfusion may activate sustained ROS production by this mechanism after RET-driven ROS production has ceased.
[Mh] Termos MeSH primário: Complexo II de Transporte de Elétrons/metabolismo
Mitocôndrias Cardíacas/metabolismo
Modelos Moleculares
Espécies Reativas de Oxigênio/agonistas
[Mh] Termos MeSH secundário: Alameticina/farmacologia
Animais
Sítios de Ligação
Ligação Competitiva
Biocatálise/efeitos dos fármacos
Sinalização do Cálcio/efeitos dos fármacos
Transporte de Elétrons/efeitos dos fármacos
Complexo II de Transporte de Elétrons/antagonistas & inibidores
Complexo II de Transporte de Elétrons/química
Inibidores Enzimáticos/farmacologia
Fumaratos/metabolismo
Ionóforos/farmacologia
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Mitocôndrias Cardíacas/química
Mitocôndrias Cardíacas/efeitos dos fármacos
Oxirredução
Permeabilidade/efeitos dos fármacos
Polienos/farmacologia
Porosidade
Piridonas/farmacologia
Coelhos
Espécies Reativas de Oxigênio/metabolismo
Ácido Succínico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Fumarates); 0 (Ionophores); 0 (Polyenes); 0 (Pyridones); 0 (Reactive Oxygen Species); 119509-24-9 (atpenin A5); 27061-78-5 (Alamethicin); 91682-96-1 (stigmatellin); AB6MNQ6J6L (Succinic Acid); EC 1.3.5.1 (Electron Transport Complex II)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180205
[Lr] Data última revisão:
180205
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.768325


  4 / 11329 MEDLINE  
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[PMID]:29267372
[Au] Autor:Hauck L; Stanley-Hasnain S; Fung A; Grothe D; Rao V; Mak TW; Billia F
[Ad] Endereço:Toronto General Research Institute, Toronto, Ontario, Canada.
[Ti] Título:Cardiac-specific ablation of the E3 ubiquitin ligase Mdm2 leads to oxidative stress, broad mitochondrial deficiency and early death.
[So] Source:PLoS One;12(12):e0189861, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The maintenance of normal heart function requires proper control of protein turnover. The ubiquitin-proteasome system is a principal regulator of protein degradation. Mdm2 is the main E3 ubiquitin ligase for p53 in mitotic cells thereby regulating cellular growth, DNA repair, oxidative stress and apoptosis. However, which of these Mdm2-related activities are preserved in differentiated cardiomyocytes has yet to be determined. We sought to elucidate the role of Mdm2 in the control of normal heart function. We observed markedly reduced Mdm2 mRNA levels accompanied by highly elevated p53 protein expression in the hearts of wild type mice subjected to myocardial infarction or trans-aortic banding. Accordingly, we generated conditional cardiac-specific Mdm2 gene knockout (Mdm2f/f;mcm) mice. In adulthood, Mdm2f/f;mcm mice developed spontaneous cardiac hypertrophy, left ventricular dysfunction with early mortality post-tamoxifen. A decreased polyubiquitination of myocardial p53 was observed, leading to its stabilization and activation, in the absence of acute stress. In addition, transcriptomic analysis of Mdm2-deficient hearts revealed that there is an induction of E2f1 and c-Myc mRNA levels with reduced expression of the Pgc-1a/Ppara/Esrrb/g axis and Pink1. This was associated with a significant degree of cardiomyocyte apoptosis, and an inhibition of redox homeostasis and mitochondrial bioenergetics. All these processes are early, Mdm2-associated events and contribute to the development of pathological hypertrophy. Our genetic and biochemical data support a role for Mdm2 in cardiac growth control through the regulation of p53, the Pgc-1 family of transcriptional coactivators and the pivotal antioxidant Pink1.
[Mh] Termos MeSH primário: Miocárdio/metabolismo
Estresse Oxidativo
Proteínas Proto-Oncogênicas c-mdm2/genética
[Mh] Termos MeSH secundário: Animais
Apoptose
Ecocardiografia
Seres Humanos
Camundongos
Camundongos Endogâmicos C57BL
Microscopia de Fluorescência
Mitocôndrias Cardíacas/enzimologia
RNA Mensageiro/genética
Reação em Cadeia da Polimerase em Tempo Real
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Proteína Supressora de Tumor p53/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (RNA, Messenger); 0 (Tumor Suppressor Protein p53); EC 2.3.2.27 (MDM2 protein, human); EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189861


  5 / 11329 MEDLINE  
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[PMID]:29175209
[Au] Autor:Wu X; Pan B; Wang Y; Liu L; Huang X; Tian J
[Ad] Endereço:Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, PR China.
[Ti] Título:The protective role of low-concentration alcohol in high-fructose induced adverse cardiovascular events in mice.
[So] Source:Biochem Biophys Res Commun;495(1):1403-1410, 2018 01 01.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cardiovascular disease remains a worldwide public health issue. As fructose consumption is dramatically increasing, it has been demonstrated that a fructose-rich intake would increase the risk of cardiovascular disease. In addition, emerging evidences suggest that low concentration alcohol intake may exert a protective effect on cardiovascular system. This study aimed to investigate whether low-concentration alcohol consumption would prevent the adverse effects on cardiovascular events induced by high fructose in mice. From the results of hematoxylin-eosin staining, echocardiography, heart weight/body weight ratio and the expression of hypertrophic marker ANP, we found high-fructose result in myocardial hypertrophy and the low-concentration alcohol consumption would prevent the cardiomyocyte hypertrophy from happening. In addition, we observed low-concentration alcohol consumption could inhibit mitochondria swollen induced by high-fructose. The elevated levels of glucose, triglyceride, total cholesterol in high-fructose group were reduced by low concentration alcohol. Low expression levels of SIRT1 and PPAR-γ induced by high-fructose were significantly elevated when fed with low-concentration alcohol. The histone lysine 9 acetylation (acH3K9) level was decreased in PPAR-γ promoter in high-fructose group but elevated when intake with low concentration alcohol. The binding levels of histone deacetylase SIRT1 were increased in the same region in high-fructose group, while the low concentration alcohol can prevent the increased binding levels. Overall, our study indicates that low-concentration alcohol consumption could inhibit high-fructose related myocardial hypertrophy, cardiac mitochondria damaged and disorders of glucose-lipid metabolism. Furthermore, these findings also provide new insights into histone acetylation-deacetylation mechanisms of low-concentration alcohol treatment that may contribute to the prevention of cardiovascular disease induced by high-fructose intake.
[Mh] Termos MeSH primário: Cardiomegalia/etiologia
Cardiomegalia/prevenção & controle
Cardiotônicos/administração & dosagem
Etanol/administração & dosagem
Frutose/efeitos adversos
Mitocôndrias Cardíacas/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Cardiomegalia/fisiopatologia
Açúcares da Dieta/efeitos adversos
Relação Dose-Resposta a Droga
Interações Medicamentosas
Frutose/administração & dosagem
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Mitocôndrias Cardíacas/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cardiotonic Agents); 0 (Dietary Sugars); 30237-26-4 (Fructose); 3K9958V90M (Ethanol)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE


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[PMID]:28450391
[Au] Autor:Korge P; Calmettes G; John SA; Weiss JN
[Ad] Endereço:From the UCLA Cardiovascular Research Laboratory and the Departments of Medicine (Cardiology) and Physiology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095.
[Ti] Título:Reactive oxygen species production induced by pore opening in cardiac mitochondria: The role of complex III.
[So] Source:J Biol Chem;292(24):9882-9895, 2017 06 16.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recent evidence has implicated succinate-driven reverse electron transport (RET) through complex I as a major source of damaging reactive oxygen species (ROS) underlying reperfusion injury after prolonged cardiac ischemia. However, this explanation may be incomplete, because RET on reperfusion is self-limiting and therefore transient. RET can only generate ROS when mitochondria are well polarized, and it ceases when permeability transition pores (PTP) open during reperfusion. Because prolonged ischemia/reperfusion also damages electron transport complexes, we investigated whether such damage could lead to ROS production after PTP opening has occurred. Using isolated cardiac mitochondria, we demonstrate a novel mechanism by which antimycin-inhibited complex III generates significant amounts of ROS in the presence of Mg and NAD and the absence of exogenous substrates upon inner membrane pore formation by alamethicin or Ca -induced PTP opening. We show that H O production under these conditions is related to Mg -dependent NADH generation by malic enzyme. H O production is blocked by stigmatellin, indicating its origin from complex III, and by piericidin, demonstrating the importance of NADH-related ubiquinone reduction for ROS production under these conditions. For maximal ROS production, the rate of NADH generation has to be equal or below that of NADH oxidation, as further increases in [NADH] elevate ubiquinol-related complex III reduction beyond the optimal range for ROS generation. These results suggest that if complex III is damaged during ischemia, PTP opening may result in succinate/malate-fueled ROS production from complex III due to activation of malic enzyme by increases in matrix [Mg ], [NAD ], and [ADP].
[Mh] Termos MeSH primário: Complexo III da Cadeia de Transporte de Elétrons/metabolismo
Malato Desidrogenase/metabolismo
Mitocôndrias Cardíacas/metabolismo
Espécies Reativas de Oxigênio/agonistas
[Mh] Termos MeSH secundário: Difosfato de Adenosina/metabolismo
Alameticina/farmacologia
Animais
Antimicina A/análogos & derivados
Antimicina A/farmacologia
Biocatálise/efeitos dos fármacos
Sinalização do Cálcio/efeitos dos fármacos
Complexo III da Cadeia de Transporte de Elétrons/antagonistas & inibidores
Ativação Enzimática/efeitos dos fármacos
Inibidores Enzimáticos/farmacologia
Peróxido de Hidrogênio/metabolismo
Ionóforos/farmacologia
Magnésio/metabolismo
Malato Desidrogenase/química
Mitocôndrias Cardíacas/química
Mitocôndrias Cardíacas/efeitos dos fármacos
NAD/metabolismo
Oxirredução
Polienos/farmacologia
Porosidade/efeitos dos fármacos
Piridinas/farmacologia
Coelhos
Espécies Reativas de Oxigênio/metabolismo
Ubiquinona/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Ionophores); 0 (Polyenes); 0 (Pyridines); 0 (Reactive Oxygen Species); 0U46U6E8UK (NAD); 11118-72-2 (antimycin); 1339-63-5 (Ubiquinone); 27061-78-5 (Alamethicin); 61D2G4IYVH (Adenosine Diphosphate); 642-15-9 (Antimycin A); 8VT513UJ9R (piericidin A); 91682-96-1 (stigmatellin); BBX060AN9V (Hydrogen Peroxide); EC 1.1.1.37 (Malate Dehydrogenase); EC 1.10.2.2 (Electron Transport Complex III); I38ZP9992A (Magnesium)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171228
[Lr] Data última revisão:
171228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.768317


  7 / 11329 MEDLINE  
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[PMID]:29252954
[Au] Autor:Vollmer JP; Haen S; Wolburg H; Lehmann R; Steiner J; Reddersen S; Fend F; Fallier-Becker P
[Ad] Endereço:Institute of Anaesthesiology, Klinikum Stuttgart, Germany.
[Ti] Título:Propofol Related Infusion Syndrome: Ultrastructural Evidence for a Mitochondrial Disorder.
[So] Source:Crit Care Med;46(1):e91-e94, 2018 Jan.
[Is] ISSN:1530-0293
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The objective of this report of a fatal propofol-related infusion syndrome in a young adult was to present-to our knowledge for the first time-direct ultrastructural evidence for the central role of mitochondrial damage in the pathogenesis of this syndrome. DATA SOURCES: Histological and electron microscopical analysis of liver, skeletal, and heart muscle obtained by autopsy and blood obtained from patient. STUDY SELECTION: Case report. DATA EXTRACTION: In addition to conventional macroscopical and histological investigations, electron-microscopical analysis of myocardial- and skeletal muscle and liver tissue obtained at autopsy from a young man was performed in order to search for ultrastructural changes of mitochondria. Acylcarnitine concentrations of his blood were determined by ultra-high performance liquid chromatography mass spectrometry. DATA SYNTHESIS: A 19-year-old male was admitted with acute left-side hemiparesis. The patient was intubated, then propofol infusion started, and a craniotomy was performed to remove an intracerebral hematoma. In the postoperative period, the patient presented with elevated intracranial pressure and brain edema. After repeat surgery, the patient showed impaired systolic left ventricular function, increasing fever, anuria, hyperkalemia, and metabolic acidosis, and he finally expired. Electron microscopy revealed dark, electron dense amorphous structures associated with mitochondria in heart muscle and liver tissue obtained at autopsy. Peripheral blood analysis revealed increased levels of acetyl-, propionyl-, butyryl-, malonyl-, and valeryl-carnitine as an indicator for propofol-related infusion syndrome, as well as for propofol-mediated inhibition of free fatty acid uptake into mitochondria, affecting beta-oxidation. CONCLUSIONS: Electron dense bodies found in association with mitochondria in muscle and liver cells probably correspond to accumulation of free fatty acid provide direct morphological evidence for the mitochondrial damage in propofol-related infusion syndrome.
[Mh] Termos MeSH primário: Doenças Mitocondriais/induzido quimicamente
Doenças Mitocondriais/patologia
Síndrome da Infusão de Propofol/patologia
[Mh] Termos MeSH secundário: Carnitina/análogos & derivados
Carnitina/sangue
Craniotomia
Hematoma Subdural Intracraniano/cirurgia
Seres Humanos
Infusões Intravenosas
Masculino
Microscopia Eletrônica
Mitocôndrias Cardíacas/efeitos dos fármacos
Mitocôndrias Cardíacas/patologia
Mitocôndrias Hepáticas/efeitos dos fármacos
Mitocôndrias Hepáticas/patologia
Mitocôndrias Musculares/efeitos dos fármacos
Mitocôndrias Musculares/patologia
Complicações Pós-Operatórias/induzido quimicamente
Complicações Pós-Operatórias/patologia
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (acylcarnitine); S7UI8SM58A (Carnitine)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171227
[Lr] Data última revisão:
171227
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171219
[St] Status:MEDLINE
[do] DOI:10.1097/CCM.0000000000002802


  8 / 11329 MEDLINE  
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[PMID]:29242353
[Au] Autor:Uchihashi M; Hoshino A; Okawa Y; Ariyoshi M; Kaimoto S; Tateishi S; Ono K; Yamanaka R; Hato D; Fushimura Y; Honda S; Fukai K; Higuchi Y; Ogata T; Iwai-Kanai E; Matoba S
[Ad] Endereço:From the Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Japan (M.U., A.H., Y.O., M.A., S.K., S.T., K.O., R.Y., D.H., Y.F., S.H., K.F., Y.H., T.O., E.I.-K., S.M.); and the Faculty of Health Care, Tenri Health Care University, Nara, Japan (E.I.-K.).
[Ti] Título:Cardiac-Specific Bdh1 Overexpression Ameliorates Oxidative Stress and Cardiac Remodeling in Pressure Overload-Induced Heart Failure.
[So] Source:Circ Heart Fail;10(12), 2017 Dec.
[Is] ISSN:1941-3297
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Energy starvation and the shift of energy substrate from fatty acids to glucose is the hallmark of metabolic remodeling during heart failure progression. However, ketone body metabolism in the failing heart has not been fully investigated. METHODS AND RESULTS: Microarray data analysis and mitochondrial isobaric tags for relative and absolute quantification proteomics revealed that the expression of D-ß-hydroxybutyrate dehydrogenase I (Bdh1), an enzyme that catalyzes the NAD /NADH coupled interconversion of acetoacetate and ß-hydroxybutyrate, was increased 2.5- and 2.8-fold, respectively, in the heart after transverse aortic constriction. In addition, ketone body oxidation was upregulated 2.2-fold in transverse aortic constriction hearts, as determined by the amount of CO released from the metabolism of [1- C] ß-hydroxybutyrate in isolated perfused hearts. To investigate the significance of this augmented ketone body oxidation, we generated heart-specific Bdh1-overexpressing transgenic mice to recapitulate the observed increase in basal ketone body oxidation. Bdh1 transgenic mice showed a 1.7-fold increase in ketone body oxidation but did not exhibit any differences in other baseline characteristics. When subjected to transverse aortic constriction, Bdh1 transgenic mice were resistant to fibrosis, contractile dysfunction, and oxidative damage, as determined by the immunochemical detection of carbonylated proteins and histone acetylation. Upregulation of Bdh1 enhanced antioxidant enzyme expression. In our in vitro study, flow cytometry revealed that rotenone-induced reactive oxygen species production was decreased by adenovirus-mediated Bdh1 overexpression. Furthermore, hydrogen peroxide-induced apoptosis was attenuated by Bdh1 overexpression. CONCLUSIONS: We demonstrated that ketone body oxidation increased in failing hearts, and increased ketone body utilization decreased oxidative stress and protected against heart failure.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica
Insuficiência Cardíaca/genética
Hidroxibutirato Desidrogenase/genética
Mitocôndrias Cardíacas/genética
Estresse Oxidativo
Pressão Ventricular/fisiologia
Remodelação Ventricular/genética
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Genótipo
Insuficiência Cardíaca/enzimologia
Insuficiência Cardíaca/fisiopatologia
Hidroxibutirato Desidrogenase/biossíntese
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Mitocôndrias Cardíacas/metabolismo
Reação em Cadeia da Polimerase
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 1.1.1.30 (Hydroxybutyrate Dehydrogenase)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171227
[Lr] Data última revisão:
171227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE


  9 / 11329 MEDLINE  
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[PMID]:28965951
[Au] Autor:Zhang M; Wang S; Cheng Z; Xiong Z; Lv J; Yang Z; Li T; Jiang S; Gu J; Sun D; Fan Y
[Ad] Endereço:Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China; Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
[Ti] Título:Polydatin ameliorates diabetic cardiomyopathy via Sirt3 activation.
[So] Source:Biochem Biophys Res Commun;493(3):1280-1287, 2017 Nov 25.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Diabetic cardiomyopathy is identified as cardiac ventricular dysfunction induced by an insulin shortage in diabetic patients. Our previous studies have shown that Polydatin (PD) alleviates cardiac dysfunction after myocardial infarction (MI) injury. Nevertheless, the mechanism by which PD regulates diabetic cardiomyopathy has not been reported. METHODS: In this study, we demonstrated the effects and described the mechanisms of PD in diabetic cardiomyopathy in both adult mouse hearts and neonatal mouse cardiomyocytes. We injected streptozotocin (STZ) to induce the DM model in wild-type (WT) and Sirt3 knockout (Sirt3 ) mice. Mitochondrial bioenergetics in diabetic mice were detected by measuring citrate synthase activity and ATP content. The extent of autophagy regulation by PD was investigated by detecting the levels of Beclin 1, Atg5, LC3 and p62. RESULTS: Compared to the WT mouse hearts, hearts from the diabetic mice exhibited better cardiac function and a higher level of autophagy. Moreover, mitochondrial function in the diabetic mouse hearts was improved after PD treatment. However, PD treatment had no effect on the Sirt3 knockout diabetic mouse hearts. Additionally, PD increased autophagy flux in the cardiomyocytes that were cultured in high-glucose medium for 48 h. In addition, PD had no effects on the cardiomyocytes under high-glucose conditions when we down-regulated Sirt3. CONCLUSIONS: Altogether, PD attenuated cardiac dysfunction, increased autophagy flux and improved mitochondrial bioenergetics by up-regulating Sirt3 in the diabetic mice.
[Mh] Termos MeSH primário: Cardiomiopatias Diabéticas/tratamento farmacológico
Glucosídeos/farmacologia
Sirtuína 3/metabolismo
Estilbenos/farmacologia
[Mh] Termos MeSH secundário: Animais
Autofagossomos/efeitos dos fármacos
Autofagia/efeitos dos fármacos
Cardiotônicos/farmacologia
Cardiomiopatias Diabéticas/metabolismo
Cardiomiopatias Diabéticas/fisiopatologia
Camundongos Endogâmicos C57BL
Camundongos Knockout
Mitocôndrias Cardíacas/efeitos dos fármacos
Mitocôndrias Cardíacas/ultraestrutura
Miócitos Cardíacos/efeitos dos fármacos
Miócitos Cardíacos/patologia
Sirtuína 3/genética
Regulação para Cima/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cardiotonic Agents); 0 (Glucosides); 0 (Sirt3 protein, mouse); 0 (Stilbenes); EC 3.5.1.- (Sirtuin 3); XM261C37CQ (polydatin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171003
[St] Status:MEDLINE


  10 / 11329 MEDLINE  
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[PMID]:28867191
[Au] Autor:Stöckigt F; Beiert T; Knappe V; Baris OR; Wiesner RJ; Clemen CS; Nickenig G; Andrié RP; Schrickel JW
[Ad] Endereço:Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany. Electronic address: florian.stoeckigt@ukbonn.de.
[Ti] Título:Aging-related mitochondrial dysfunction facilitates the occurrence of serious arrhythmia after myocardial infarction.
[So] Source:Biochem Biophys Res Commun;493(1):604-610, 2017 Nov 04.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: During aging a mosaic of normal cells and cells with mitochondrial deficiency develops in various tissues including the heart. Whether this contributes to higher susceptibility for arrhythmia following myocardial infarction (MI) is unknown. METHODS AND RESULTS: Myocardial cryoinfarction was performed in 12-month-old transgenic mice with accelerated accumulation of deletions in mitochondrial DNA. Occurrence and pathogenesis of arrhythmia was investigated after two weeks. Holter-ECG recordings revealed higher rates of premature ventricular complexes (incidence > 10/24 h: 100% vs. 20%; p = 0.048) and more severe spontaneous arrhythmia during stress test in mutant mice with MI as compared to control mice with MI. Mice with mitochondrial dysfunction exhibited longer spontaneous AV-blocks (467 ± 26 ms vs. 377 ± 24 ms; p = 0.013), an increased probability for induction of ventricular tachycardia during in vivo electrophysiological investigation (22% vs. 9%; p = 0.044), and a reduced conduction velocity in the infarct borderzone (38.5 ± 0.5 cm/s vs. 55.3 ± 0.9 cm/s; p = 0.001). Furthermore, mutant mice exhibited a significant reduction of the phospho-Cx43/Cx43 ratio in right (0.59 ± 0.04 vs. 0.85 ± 0.01; p = 0.027) and left ventricular myocardium (0.72 ± 0.01 vs. 0.86 ± 0.02; p = 0.023). CONCLUSIONS: Aging-related cardiac mosaic respiratory chain dysfunction facilitates the occurrence of spontaneous and inducible cardiac arrhythmia after myocardial infarction and is associated with slowing of electrical impulse propagation in the infarct borderzone.
[Mh] Termos MeSH primário: Envelhecimento
Arritmias Cardíacas/etiologia
Arritmias Cardíacas/fisiopatologia
Sistema de Condução Cardíaco/fisiopatologia
Mitocôndrias Cardíacas
Doenças Mitocondriais/fisiopatologia
Infarto do Miocárdio/fisiopatologia
[Mh] Termos MeSH secundário: Animais
Feminino
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Doenças Mitocondriais/complicações
Infarto do Miocárdio/complicações
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170905
[St] Status:MEDLINE



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