Title |
CD38 Causes Autophagic Flux Inhibition and Cardiac Dysfunction Through a Transcriptional Inhibition Pathway Under Hypoxia/Ischemia Conditions
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Published in |
Frontiers in Cell and Developmental Biology, April 2020
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DOI | 10.3389/fcell.2020.00191 |
Pubmed ID | |
Authors |
Xingyue Zhang, Lingfei Li, Qiong Zhang, Qinglin Wei, Jiezhi Lin, Jiezhi Jia, Junhui Zhang, Tiantian Yan, Yanling Lv, Xupin Jiang, Peng Zhang, Huapei Song, Dongxia Zhang, Yuesheng Huang |
Abstract |
Induced autophagy is protective against myocardial hypoxia/ischemia (H/I) injury, but evidence regarding the extent of autophagic clearance under H/I and the molecular mechanisms that influence autophagic flux has scarcely been presented. Here, we report that CD38 knockout improved cardiac function and autophagic flux in CD38-/- mice and CD38-/- neonatal cardiomyocytes (CMs) under H/I conditions. Mechanistic studies demonstrated that overexpression of CD38 specifically downregulated the expression of Rab7 and its adaptor protein pleckstrin homology domain-containing protein family member 1 (PLEKHM1) through nicotinamide adenine dinucleotide (NAD)-dependent and non-NAD-dependent pathways, respectively. Loss of Rab7/PLEKHM1 impaired the fusion of autophagosomes and lysosomes, resulting in autophagosome accumulation in the myocardium and consequent cardiac dysfunction under H/I conditions. Thus, CD38 mediated autophagic flux blockade and cardiac dysfunction in a Rab7/PLEKHM1-dependent manner. These findings suggest a potential therapeutic strategy involving targeted suppression of CD38 expression. |
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Unknown | 2 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
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Unknown | 19 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Doctoral Student | 4 | 21% |
Student > Ph. D. Student | 3 | 16% |
Researcher | 3 | 16% |
Other | 2 | 11% |
Student > Master | 1 | 5% |
Other | 3 | 16% |
Unknown | 3 | 16% |
Readers by discipline | Count | As % |
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Pharmacology, Toxicology and Pharmaceutical Science | 3 | 16% |
Biochemistry, Genetics and Molecular Biology | 2 | 11% |
Immunology and Microbiology | 1 | 5% |
Chemistry | 1 | 5% |
Other | 0 | 0% |
Unknown | 6 | 32% |