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• W4294607140 abstract "Abstract Autophagy is a self‐degradation process of cytoplasmic components and occurs in the failing heart. Angiotensin II plays a critical role in the progression of heart failure and induces autophagy. We investigated the mechanism underlying angiotensin II‐enhanced autophagy and examined the role of autophagy in angiotensin II‐induced cardiomyocyte injury. Neonatal rat cardiomyocytes were treated with angiotensin II (1–100 nmol/L). Angiotensin II dose‐dependently increased autophagy indicators of microtubule‐associated protein 1 light chain (LC) 3‐II and monodansylcadaverine‐labelled vesicles. It also enhanced the intracellular production of reactive oxygen species (ROS), assessed by H2DCFDA, an intracellular ROS indicator. NADPH oxidase‐ and mitochondria‐derived ROS production was increased by angiotensin II, while angiotensin II‐induced LC3‐II expression was suppressed by inhibitors of these sources of ROS. Confocal microscopy revealed that superoxide‐producing mitochondria colocalized with lysosomes after the angiotensin II stimulation. Myocyte apoptosis was assessed by nuclear staining with DAPI and caspase‐3 activity. A 6‐h stimulation with angiotensin II did not affect myocyte apoptosis, while a co‐treatment with 3‐methyl‐adenine (3MA), an autophagy inhibitor, augmented apoptosis. These results indicate that autophagy suppressed apoptosis because it removed damaged mitochondria in the early stages of the angiotensin II stimulation. A longer angiotensin II stimulation for 24 h induced apoptosis and propidium iodide‐positive lethal myocytes, while the co‐treatment with 3MA did not lead to further increases. In conclusion, angiotensin II‐induced autophagy removes ROS‐producing mitochondria. Autophagy is a beneficial phenomenon against myocyte apoptosis in the early phase, but its benefit was limited in the late phase of angiotensin II stimulation." @default.
• W4294607140 created "2022-09-05" @default.
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• W4294607140 date "2022-09-18" @default.
• W4294607140 modified "2023-09-26" @default.
• W4294607140 title "Roles of autophagy in angiotensin <scp>II</scp>‐induced cardiomyocyte apoptosis" @default.
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• W4294607140 doi "https://doi.org/10.1111/1440-1681.13719" @default.
• W4294607140 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36059129" @default.
• W4294607140 hasPublicationYear "2022" @default.
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