Cardiac Plin5 interacts with SERCA2 and promotes calcium handling and cardiomyocyte contractility.

Autor:	Cinato M; Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburgand Sahlgrenska University Hospital, Gothenburg, Sweden., Mardani I; Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburgand Sahlgrenska University Hospital, Gothenburg, Sweden., Miljanovic A; Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburgand Sahlgrenska University Hospital, Gothenburg, Sweden., Drevinge C; Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburgand Sahlgrenska University Hospital, Gothenburg, Sweden., Laudette M; Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburgand Sahlgrenska University Hospital, Gothenburg, Sweden., Bollano E; Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburgand Sahlgrenska University Hospital, Gothenburg, Sweden., Henricsson M; Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburgand Sahlgrenska University Hospital, Gothenburg, Sweden., Tolö J; Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden., Bauza Thorbrügge M; Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden., Levin M; Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburgand Sahlgrenska University Hospital, Gothenburg, Sweden malin.levin@wlab.gu.se., Lindbom M; Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburgand Sahlgrenska University Hospital, Gothenburg, Sweden., Arif M; Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA., Pacher P; Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA., Andersson L; Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburgand Sahlgrenska University Hospital, Gothenburg, Sweden., Olofsson CS; Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden., Borén J; Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburgand Sahlgrenska University Hospital, Gothenburg, Sweden., Levin MC; Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburgand Sahlgrenska University Hospital, Gothenburg, Sweden malin.levin@wlab.gu.se.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2023 Jan 30; Vol. 6 (4). Date of Electronic Publication: 2023 Jan 30 (Print Publication: 2023).
DOI:	10.26508/lsa.202201690
Abstrakt:	The adult heart develops hypertrophy to reduce ventricular wall stress and maintain cardiac function in response to an increased workload. Although pathological hypertrophy generally progresses to heart failure, physiological hypertrophy may be cardioprotective. Cardiac-specific overexpression of the lipid-droplet protein perilipin 5 (Plin5) promotes cardiac hypertrophy, but it is unclear whether this response is beneficial. We analyzed RNA-sequencing data from human left ventricle and showed that cardiac PLIN5 expression correlates with up-regulation of cardiac contraction-related processes. To investigate how elevated cardiac Plin5 levels affect cardiac contractility, we generated mice with cardiac-specific overexpression of Plin5 (MHC- Plin5 mice). These mice displayed increased left ventricular mass and cardiomyocyte size but preserved heart function. Quantitative proteomics identified sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase 2 (SERCA2) as a Plin5-interacting protein. In situ proximity ligation assay further confirmed the Plin5/SERCA2 interaction. Live imaging showed increases in intracellular Ca 2+ release during contraction, Ca 2+ removal during relaxation, and SERCA2 function in MHC- Plin5 versus WT cardiomyocytes. These results identify a role of Plin5 in improving cardiac contractility through enhanced Ca 2+ signaling. (© 2023 Cinato et al.)
Databáze:	MEDLINE
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