Frontiers in Cell and Developmental Biology (Apr 2020)
CD38 Causes Autophagic Flux Inhibition and Cardiac Dysfunction Through a Transcriptional Inhibition Pathway Under Hypoxia/Ischemia Conditions
- Xingyue Zhang,
- Xingyue Zhang,
- Lingfei Li,
- Lingfei Li,
- Qiong Zhang,
- Qiong Zhang,
- Qinglin Wei,
- Jiezhi Lin,
- Jiezhi Lin,
- Jiezhi Jia,
- Jiezhi Jia,
- Junhui Zhang,
- Junhui Zhang,
- Tiantian Yan,
- Yanling Lv,
- Yanling Lv,
- Xupin Jiang,
- Xupin Jiang,
- Peng Zhang,
- Peng Zhang,
- Huapei Song,
- Huapei Song,
- Dongxia Zhang,
- Dongxia Zhang,
- Yuesheng Huang,
- Yuesheng Huang,
- Yuesheng Huang
Affiliations
- Xingyue Zhang
- Institute of Burn Research, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Xingyue Zhang
- State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Lingfei Li
- Institute of Burn Research, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Lingfei Li
- State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Qiong Zhang
- Institute of Burn Research, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Qiong Zhang
- State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Qinglin Wei
- Cholestatic Liver Diseases Center of the Institute of Digestive Disease, First Affiliated of Army Medical University, Chongqing, China
- Jiezhi Lin
- Institute of Burn Research, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Jiezhi Lin
- State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Jiezhi Jia
- Institute of Burn Research, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Jiezhi Jia
- State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Junhui Zhang
- Institute of Burn Research, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Junhui Zhang
- State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Tiantian Yan
- Military Burn Center, The 990th (159th) Hospital of the People’s Liberation Army, Zhumadian, China
- Yanling Lv
- Institute of Burn Research, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Yanling Lv
- State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Xupin Jiang
- Institute of Burn Research, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Xupin Jiang
- State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Peng Zhang
- Institute of Burn Research, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Peng Zhang
- State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Huapei Song
- Institute of Burn Research, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Huapei Song
- State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Dongxia Zhang
- Institute of Burn Research, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Dongxia Zhang
- State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Yuesheng Huang
- Institute of Burn Research, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Yuesheng Huang
- State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Army Medical University, Third Military Medical University, Chongqing, China
- Yuesheng Huang
- Department of Wound Repair, Institute of Wound Repair, The First Affiliated Hospital of South University of Science and Technology (Shenzhen Peoples Hospital), Shenzhen, China
- DOI
- https://doi.org/10.3389/fcell.2020.00191
- Journal volume & issue
-
Vol. 8
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.
Keywords
- pleckstrin homology domain-containing protein family member 1
- Rab7
- nicotinamide adenine dinucleotide
- autophagosome–lysosome fusion
- heart disease