H(+)/Cl(-) exchange transporter 7 promotes lysosomal acidification-mediated autophagy in mouse cardiomyocytes

Lin，Jiezhi1,2; Wei，Jinyu1,3; Lv，Yanling1; Zhang，Xingyue1; Yi，Ruo Fan1; Dai，Chen4; Zhang，Qiong1; Jia，Jiezhi1; Zhang，Dongxia1; Huang，Yuesheng1,5

2021

10.3892/MMR.2021.11861

Molecular Medicine Reports   Impact Factor & Quartile

1791-2997

1791-3004

Autophagy protects cardiomyocytes in various pathological and physiological conditions; however, the molec- ular mechanisms underlying its influence and the promotion of autophagic clearance are not completely understood. The present study aimed to explore the role of H(+)/Cl(-) exchange transporter 7 (CLC-7) in cardiomyocyte autophagy. In this study, rapamycin was used to induce autophagy in mouse cardiomyocytes, and the changes in CLC-7 were investi- gated. The expression levels of CLC-7 and autophagy-related proteins, such as microtubule associated protein 1 light chain 3, autophagy related 5 and Beclin 1, were detected using western blotting or immunofluorescence. Autolysosomes were observed and analyzed using transmission electron micros- copy and immunofluorescence following CLC-7 silencing with small interfering RNAs. Cellular viability was assessed using Cell Counting Kit-8 and lactate dehydrogenase assays. Lysosomal acidification was measured using an acidification indicator. Increased CLC-7 co-localization with lysosomes was identified during autophagy. CLC-7 knockdown weak- ened the acidification of lysosomes, which are the terminal compartments of autophagy flux, and consequently impaired autophagy flux, ultimately resulting in cell injury. Collectively, the present study demonstrated that in cardiomyocytes, CLC-7 may contribute to autophagy via regulation of lysosomal acidi- fication. These findings provide novel insights into the role of CLC-7 in autophagy and cytoprotection.

Autophagy Cardiomyocyte CLC-7 Lysosomal acidification Rapamycin

SCI

English

Others

WOS:000613736700001

2-s2.0-85100466450

Scopus

1.Institute of Burn Research,State Key Laboratory of Trauma,Burns and Combined Injury,Southwest Hospital,Third Military Medical University,Chongqing,400038,China
2.Military Burn Center,963rd (224th) Hospital of People's Liberation Army,963rd,Hospital of Joint Logistics Support Force of PLA,Jiamusi, Heilongjiang,154007,China
3.Dermatology Department,920th Hospital of People's Liberation Army,920th Hospital of Joint Logistics Support Force of PLA,Kunming, Yunnan,650100,China
4.Orthopedics and Trauma Department,963rd (224th) Hospital of People's Liberation Army,963rd,Hospital of Joint Logistics Support Force of PLA,Jiamusi, Heilongjiang,154007,China
5.Department of Wound Repair,Institute of Wound Repair,Shenzhen People's Hospital,First Affiliated Hospital of Southern University of Science and Technology,Second Clinical Medical College of Jinan University,Shenzhen, Guangdong,518020,China

Lin，Jiezhi,Wei，Jinyu,Lv，Yanling,et al. H(+)/Cl(-) exchange transporter 7 promotes lysosomal acidification-mediated autophagy in mouse cardiomyocytes[J]. Molecular Medicine Reports,2021,23(3).

Lin，Jiezhi.,Wei，Jinyu.,Lv，Yanling.,Zhang，Xingyue.,Yi，Ruo Fan.,...&Huang，Yuesheng.(2021).H(+)/Cl(-) exchange transporter 7 promotes lysosomal acidification-mediated autophagy in mouse cardiomyocytes.Molecular Medicine Reports,23(3).

Lin，Jiezhi,et al."H(+)/Cl(-) exchange transporter 7 promotes lysosomal acidification-mediated autophagy in mouse cardiomyocytes".Molecular Medicine Reports 23.3(2021).