Critical appraisal of STAT3 pattern in adult cardiomyocytes

Autor: Emmanuelle Canet-Soulas, Bruno Pillot, Noelle Gallo Bona, Mazen Kurdi, George W. Booz, Sally Badawi, Lionel Augeul, Michel Ovize, Melanie Paillard, Gabriel Bidaux, Zeina Harhous
Přispěvatelé: Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Lebanese University [Beirut] (LU), University of Mississippi Medical Center (UMMC), This work was supported by the IHU OPeRa (ANR-10-IBHU-004) within the program 'Investissements d'Avenir' operated by the French National Research Agency (ANR). Zeina Harhous was supported by the 'Association de Specialisation et d'orientation Scientifique'. Sally Badawi was supported by the Council for Scientific Research and Lebanese University fellowship (CNRS-L) program and the Eiffel scholarship program of excellence of Campus France. We acknowledge the financial support from ITMO Cancer AVIESAN (Alliance Nationale pour les Sciences de la Vie et de la Santé, National Alliance for Life Sciences and Health) within the framework of the cancer plan for Orbitrap mass spectrometer founding., ANR-10-IBHU-0004,OPeRa,Organ ProtEction and ReplAcement(2010), bidaux, gabriel, Instituts Hospitalo-Universitaires B - Organ ProtEction and ReplAcement - - OPeRa2010 - ANR-10-IBHU-0004 - IBHU - VALID, Department of Cardiology, Hospices Civils de Lyon (HCL), Institut National de la Sante et de la Recherche Medicale (Inserm), Lebanese University, Cedar program of Campus France [37303QA 2017-2018], IHU OPeRa within the program 'Investissements d'Avenir' [ANR-10-IBHU-004], Association de Spécialisation et d'orientation Scientifique, Council for Scientific Research and Lebanese University fellowship (CNRS-L) program, Eiffel scholarship program of excellence of Campus France, ITMO Cancer AVIESAN (Alliance Nationale pour les Sciences de la Vie et de la Sante, National Alliance for Life Sciences and Health), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Atropine
Male
0301 basic medicine
[SDV]Life Sciences [q-bio]
030204 cardiovascular system & hematology
Mitochondrion
Mass Spectrometry
Mitochondria
Heart
Oxidative Phosphorylation
Mice
Nitroglycerin
0302 clinical medicine
Papaverine
Myocytes
Cardiac
10. No inequality
STAT3
Mice
Knockout
Cardiomyocytes
biology
Chemistry
Ischemia-reperfusion
Brain
Aminophylline
Cell biology
Mitochondria
[SDV] Life Sciences [q-bio]
Drug Combinations
T-tubules
medicine.anatomical_structure
Liver
Phenobarbital
Cell fractionation
Cardiology and Cardiovascular Medicine
Signal Transduction
STAT3 Transcription Factor
Cell type
Myocardial Reperfusion Injury
Cell Line
03 medical and health sciences
medicine
Animals
Molecular Biology
Transcription factor
Endoplasmic reticulum
Subcellular distribution
Rats
Mice
Inbred C57BL
030104 developmental biology
Mitochondrial permeability transition pore
biology.protein
Nucleus
Mitochondria associated membranes
Zdroj: Journal of Molecular and Cellular Cardiology
Journal of Molecular and Cellular Cardiology, Elsevier, 2019, 131, pp.91-100. ⟨10.1016/j.yjmcc.2019.04.021⟩
Journal of Molecular and Cellular Cardiology, Elsevier, 2019, 131, pp.91--100. ⟨10.1016/j.yjmcc.2019.04.021⟩
ISSN: 0022-2828
1095-8584
DOI: 10.1016/j.yjmcc.2019.04.021⟩
Popis: International audience; The signal transducer and activator of transcription 3, STAT3, transfers cellular signals from the plasma membrane to the nucleus, acting as a signaling molecule and a transcription factor. Reports proposed an additional non-canonical role of STAT3 that could regulate the activity of complexes I and II of the electron transport chain and the opening of the mitochondrial permeability transition pore (PTP) after ischemia-reperfusion in various cell types. The native expression of STAT3 in heart mitochondria, together with a direct versus an indirect transcriptional role in mitochondrial functions, have been recently questioned. The objective of the present study was to investigate the cellular distribution of STAT3 in mouse adult cardiomyocytes under basal and stress conditions, along with assessing its presence and activity in cardiac mitochondria using structural and functional approaches. The analysis of the spatial distribution of STAT3 signal in the cardiomyocytes interestingly showed that it is transversely distributed along the T-tubules and in the nucleus. This distribution was neither affected by hypoxia nor by hypoxia/re-oxygenation conditions. Focusing on the mitochondrial STAT3 localization, our results suggest that serine-phosphorylated STAT3 (PS727-STAT3) and total STAT3 are detected in crude but not in pure mitochondria of mouse adult cardiomyocytes, under basal and ischemia-reperfusion conditions. The inhibition of STAT3, with a pre-validated non-toxic Stattic dose, had no significant effects on mitochondrial respiration, but a weak effect on the calcium retention capacity. Overall, our results exclusively reveal a unique cellular distribution of STAT3 in mouse adult cardiomyocytes, along the Ttubules and in nucleus, under different conditions. They also challenge the expression and activity of STAT3 in mitochondria of these cells under basal conditions and following ischemia-reperfusion. In addition, our results underline technical methods, complemental to cell fractionation, to evaluate STAT3 roles during hypoxia-reoxygenation and at the interface between nucleus and endoplasmic reticulum.
Databáze: OpenAIRE
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