title: Rcan1-1L overexpression induces mitochondrial autophagy and improves cell survival in angiotensin II-exposed cardiomyocytes.
abstract: Mitochondrial autophagy is an important adaptive stress response and can be modulated by various key molecules. A previous study found that the regulator of calcineurin 1-1L (Rcan1-1L) may regulate mitochondrial autophagy and cause mitochondria degradation in neurocytes. However, the effect of Rcan1-1L on cardiomyocytes has not been determined. In the present study, we aimed to investigate the role of Rcan1-1L in angiotensin II (Ang II)-exposed human cardiomyocytes. Above all, Human adult cardiac myocytes (HACMs) were exposed to 200nmol/L Ang II for 4 days. Enhanced H2O2 production, cytochrome C release and mitochondrial permeability were observed in these cells, which were blocked by valsartan. Consistently, Ang II exposure significantly reduced cardiomyocyte viability. However, transfection of Rcan1-1L vector promoted cell viability and ameliorated the apoptosis caused by Ang II. Rcan1-1L clearly promoted mitochondrial autophagy in HACMs, with elevated autophagy protein (ATG) 5 and light chain 3 (LC3) expression. Transient mitochondrial biogenesis and reduced cytochrome C release was also induced by Rcan1-1L. Additionally, Rcan1-1L significantly inhibited calcineurin/nuclear factor of activated T cells (NFAT) signaling. We thus conclude that Rcan1-1L may play a protective role in Ang II-treated cardiomyocytes through the induction of mitochondrial autophagy, and may be an alternative method of cardiac protection.
authors.affiliation: Department of cardiology, Henan Provincial People's Hospital, Zhengzhou 450003, PR China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Duan
authors.affiliation: Department of cardiology, Henan Provincial People's Hospital, Zhengzhou 450003, PR China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of cardiology, Henan Provincial People's Hospital, Zhengzhou 450003, PR China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of cardiology, Henan Provincial People's Hospital, Zhengzhou 450003, PR China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of cardiology, Henan Provincial People's Hospital, Zhengzhou 450003, PR China.
authors.forename: Jintao
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of cardiology, Henan Provincial People's Hospital, Zhengzhou 450003, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Qian
authors.affiliation: Department of cardiology, Henan Provincial People's Hospital, Zhengzhou 450003, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of cardiology, Henan Provincial People's Hospital, Zhengzhou 450003, PR China. Electronic address: shanglingwang@126.com.
authors.forename: Shanling
authors.initials: S
authors.lastname: Wang
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D001343:Autophagy; D000071187:Autophagy-Related Protein 5; D002470:Cell Survival; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D004268:DNA-Binding Proteins; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006973:Hypertension / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000378:metabolism; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D063306:Mitophagy / Q000187:drug effects*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects; D010539:Permeability / Q000187:drug effects
chemical_list: C502778:ATG5 protein, human; D000071187:Autophagy-Related Protein 5; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D009124:Muscle Proteins; D050778:NFATC Transcription Factors; C108612:RCAN1 protein, human; D000804:Angiotensin II; D045304:Cytochromes c; D006861:Hydrogen Peroxide
keywords: Angiotensin II exposure; Cardiac protection; Cardiomyocytes; Mitochondrial autophagy; Rcan1-1L