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13-Methylpalmatine improves myocardial infarction injury by inhibiting CHOP-mediated cross-talk between endoplasmic reticulum and mitochondria.

Authors :
Jiang Z
Wen X
Mao Q
Wang G
Wang Z
Yan Y
Gao S
Sun X
Zhang M
Liu J
Zhang R
Yang B
Source :
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Oct; Vol. 179, pp. 117342. Date of Electronic Publication: 2024 Aug 24.
Publication Year :
2024

Abstract

Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide, and endoplasmic reticulum stress (ERS) and mitochondrial Ca <superscript>2+</superscript> overload have been involved in apoptotic cardiomyocyte death during MI. 13-Methylpalmatine (13-Me-PLT) is a natural isoquinoline alkaloid isolated from Coptis chinensis and has not been systematically studied for their potential pharmacological effects in cardiovascular diseases. We conducted the present study to elucidate whether 13-Me-PLT modulates MI pathology in animal MI and cellular hypoxic models, employing state-of-the-art molecular techniques. The results demonstrated that 13-Me-PLT preserved post-ischemic cardiac function and alleviated cardiomyocyte apoptosis. 13-Me-PLT decreased ERS and the communication between ER and mitochondria, which serves as a protective mechanism against mitochondrial Ca <superscript>2+</superscript> overload and structural and functional injuries to mitochondria. Our data revealed mitigating mitochondrial Ca <superscript>2+</superscript> overload and apoptosis by inhibiting CHOP-mediated Ca <superscript>2+</superscript> transfer between inositol 1,4,5-trisphosphate receptor (IP <subscript>3</subscript> R) in ER and VDAC1 in mitochondria as an underlying mechanism for 13-Me-PLT action. Furthermore, 13-Me-PLT produced superior effects in alleviating cardiac dysfunction and apoptosis post-MI to diltiazem and palmatine. Collectively, our research suggests that the CHOP/IP <subscript>3</subscript> R/VDAC1 signaling pathway mediates ER-mitochondrial Ca <superscript>2+</superscript> transfer and 13-Me-PLT activates this axis to maintain cellular and organellar Ca <superscript>2+</superscript> homeostasis, protecting against ischemic myocardial injury. These findings may offer an opportunity to develop new agents for the therapy of ischemic heart disease.<br />Competing Interests: Declaration of Competing Interest All the authors declare no competing financial interest.<br /> (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Details

Language :
English
ISSN :
1950-6007
Volume :
179
Database :
MEDLINE
Journal :
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Publication Type :
Academic Journal
Accession number :
39182321
Full Text :
https://doi.org/10.1016/j.biopha.2024.117342