PMID- 35924992
OWN - NLM
STAT- MEDLINE
DCOM- 20221012
LR  - 20231213
IS  - 1095-8355 (Electronic)
IS  - 1065-6995 (Linking)
VI  - 46
IP  - 11
DP  - 2022 Nov
TI  - Chaperone-mediated autophagy attenuates H(2) O(2) -induced cardiomyocyte 
      apoptosis by targeting poly (ADP-ribose) polymerase 1 (PARP1) for lysosomal 
      degradation.
PG  - 1915-1926
LID - 10.1002/cbin.11871 [doi]
AB  - Poly (ADP-ribose) polymerase 1 (PARP1) is a typical representative of the PARP 
      enzyme family and is mainly related to DNA repair, gene transcription regulation, 
      inflammation, and oxidative stress. Studies have found that PARP1 is involved in 
      the pathophysiological processes of a variety of cardiovascular diseases. 
      Chaperone-mediated autophagy (CMA) is involved in the molecular regulation of 
      various diseases, including cardiovascular diseases, and plays a critical role in 
      maintaining intracellular metabolism balance. However, the link between PARP1 and 
      CMA in cardiomyocytes remains unclear. Therefore, the aims of this study were to 
      investigate whether CMA is involved in PARP1 regulation and to further clarify 
      the specific molecular mechanisms. Earle's balanced salt solution (EBSS)-induced 
      activation of autophagy reduced PARP1 expression, whereas the autophagy lysosomal 
      inhibitor CQ had the opposite effect. Correspondingly, treatment with the 
      autophagy inhibitor 3-methyladenine did not abolish the autophagy-inducing 
      effects of EBSS. Additionally, PARP1 binds to heat shock cognate protein 70 and 
      lysosome-associated membrane protein 2A (LAMP2A). Moreover, adenovirus-mediated 
      LAMP2A overexpression to activate the CMA signaling pathway in cardiomyocytes 
      reduces PARP1 (cleaved) expression and further decreases cardiomyocyte apoptosis 
      caused by oxidative stress. In contrast, downregulation of LAMP2A increased PARP1 
      (cleaved) expression and the degree of apoptosis. More importantly, we report 
      that appropriate concentrations of H(2) O(2) triggered the nuclear translocation 
      of PARP1, which subsequently promoted the degradation of PARP1 through the CMA 
      pathway. In summary, our data are the first to reveal that CMA targeted PARP1 for 
      lysosomal degradation in cardiomyocytes, which ultimately inhibited apoptosis by 
      promoting the degradation of the PARP1 protein.
CI  - (c) 2022 International Federation for Cell Biology.
FAU - Zhang, Dandan
AU  - Zhang D
AUID- ORCID: 0000-0002-0475-1114
AD  - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang 
      University, Nanchang, China.
AD  - Jiangxi Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of 
      Nanchang University, Nanchang, China.
FAU - Lai, Wei
AU  - Lai W
AD  - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang 
      University, Nanchang, China.
AD  - Jiangxi Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of 
      Nanchang University, Nanchang, China.
FAU - Liu, Yang
AU  - Liu Y
AD  - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang 
      University, Nanchang, China.
AD  - Jiangxi Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of 
      Nanchang University, Nanchang, China.
FAU - Wan, Rong
AU  - Wan R
AD  - Jiangxi Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of 
      Nanchang University, Nanchang, China.
FAU - Shen, Yang
AU  - Shen Y
AD  - Jiangxi Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of 
      Nanchang University, Nanchang, China.
AD  - Department of Genetic Medicine, The Second Affiliated Hospital of Nanchang 
      University, Nanchang, China.
LA  - eng
GR  - 21866019/National Natural Science Foundation of China/
GR  - 31860320/National Natural Science Foundation of China/
GR  - 20181BAB215030/Youth Science Foundation of Jiangxi Provincia/
PT  - Journal Article
DEP - 20220804
PL  - England
TA  - Cell Biol Int
JT  - Cell biology international
JID - 9307129
RN  - 0 (Lysosomal Membrane Proteins)
RN  - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN  - 61D2G4IYVH (Adenosine Diphosphate)
RN  - 681HV46001 (Ribose)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 2.4.2.30 (PARP1 protein, human)
RN  - EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1)
SB  - IM
MH  - Adenosine Diphosphate/metabolism
MH  - Apoptosis
MH  - Autophagy/physiology
MH  - *Cardiovascular Diseases/metabolism
MH  - *Chaperone-Mediated Autophagy
MH  - Humans
MH  - Hydrogen Peroxide/*pharmacology
MH  - Lysosomal Membrane Proteins/metabolism
MH  - Lysosomes/metabolism
MH  - Myocytes, Cardiac/metabolism
MH  - Poly (ADP-Ribose) Polymerase-1/metabolism
MH  - Poly(ADP-ribose) Polymerase Inhibitors/metabolism
MH  - Ribose/metabolism
OTO - NOTNLM
OT  - apoptosis
OT  - cardiomyocyte
OT  - chaperone-mediated autophagy
OT  - lysosomal
OT  - oxidative stress
OT  - poly (ADP-ribose) polymerase 1
EDAT- 2022/08/05 06:00
MHDA- 2022/10/13 06:00
CRDT- 2022/08/04 10:05
PHST- 2022/03/31 00:00 [received]
PHST- 2022/07/14 00:00 [accepted]
PHST- 2022/08/05 06:00 [pubmed]
PHST- 2022/10/13 06:00 [medline]
PHST- 2022/08/04 10:05 [entrez]
AID - 10.1002/cbin.11871 [doi]
PST - ppublish
SO  - Cell Biol Int. 2022 Nov;46(11):1915-1926. doi: 10.1002/cbin.11871. Epub 2022 Aug 
      4.