Protocatechuic aldehyde protects cardiomycoytes against ischemic injury via regulation of nuclear pyruvate kinase M2

Rescuing cells from stress damage emerges a potential therapeutic strategy to combat myocardial infarction. Protocatechuic aldehyde (PCA) is a major phenolic acid in Chinese herb Danshen (Salvia miltiorrhiza root). This study investigated whether PCA regulated nuclear pyruvate kinase isoform M2 (PKM...

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Autores principales:	Xunxun Wu, Lian Liu, Qiuling Zheng, Haiping Hao, Hui Ye, Ping Li, Hua Yang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Protocatechuic aldehyde PKM2 β-Catenin TCF4 Heart ischemia Myocardial infarction Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/a57b187724ad48fa880cde6ea6fada65
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spelling	oai:doaj.org-article:a57b187724ad48fa880cde6ea6fada652021-12-02T05:01:21ZProtocatechuic aldehyde protects cardiomycoytes against ischemic injury via regulation of nuclear pyruvate kinase M22211-383510.1016/j.apsb.2021.03.021https://doaj.org/article/a57b187724ad48fa880cde6ea6fada652021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211383521000939https://doaj.org/toc/2211-3835Rescuing cells from stress damage emerges a potential therapeutic strategy to combat myocardial infarction. Protocatechuic aldehyde (PCA) is a major phenolic acid in Chinese herb Danshen (Salvia miltiorrhiza root). This study investigated whether PCA regulated nuclear pyruvate kinase isoform M2 (PKM2) function to protect cardiomyocytes. In rats subjected to isoprenaline, PCA attenuated heart injury and protected cardiomyocytes from apoptosis. Through DARTS and CETSA assays, we identified that PCA bound and promoted PKM2 nuclear translocation in cardiomyocytes exposed to oxygen/glucose deprivation (OGD). In the nucleus, PCA increased the binding of PKM2 to β-catenin via preserving PKM2 acetylation, and the complex, in cooperation with T-cell factor 4 (TCF4), was required for transcriptional induction of genes encoding anti-apoptotic proteins, contributing to rescuing cardiomyocyte survival. In addition, PCA ameliorated mitochondrial dysfunction and prevented mitochondrial apoptosis dependent on PKM2. Consistently, PCA increased the binding of PKM2 to β-catenin, improved heart contractive function, normalized heart structure and attenuated oxidative damage in mice subjected to artery ligation, but the protective effects were lost in Pkm2-deficient heart. Together, we showed that PCA regulated nuclear PKM2 function to rescue cardiomyocyte survival via β-catenin/TCF4 signaling cascade, suggesting the potential of pharmacological intervention of PKM2 shuttle to protect the heart.Xunxun WuLian LiuQiuling ZhengHaiping HaoHui YePing LiHua YangElsevierarticleProtocatechuic aldehydePKM2β-CateninTCF4Heart ischemiaMyocardial infarctionTherapeutics. PharmacologyRM1-950ENActa Pharmaceutica Sinica B, Vol 11, Iss 11, Pp 3553-3566 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Protocatechuic aldehyde PKM2 β-Catenin TCF4 Heart ischemia Myocardial infarction Therapeutics. Pharmacology RM1-950
spellingShingle	Protocatechuic aldehyde PKM2 β-Catenin TCF4 Heart ischemia Myocardial infarction Therapeutics. Pharmacology RM1-950 Xunxun Wu Lian Liu Qiuling Zheng Haiping Hao Hui Ye Ping Li Hua Yang Protocatechuic aldehyde protects cardiomycoytes against ischemic injury via regulation of nuclear pyruvate kinase M2
description	Rescuing cells from stress damage emerges a potential therapeutic strategy to combat myocardial infarction. Protocatechuic aldehyde (PCA) is a major phenolic acid in Chinese herb Danshen (Salvia miltiorrhiza root). This study investigated whether PCA regulated nuclear pyruvate kinase isoform M2 (PKM2) function to protect cardiomyocytes. In rats subjected to isoprenaline, PCA attenuated heart injury and protected cardiomyocytes from apoptosis. Through DARTS and CETSA assays, we identified that PCA bound and promoted PKM2 nuclear translocation in cardiomyocytes exposed to oxygen/glucose deprivation (OGD). In the nucleus, PCA increased the binding of PKM2 to β-catenin via preserving PKM2 acetylation, and the complex, in cooperation with T-cell factor 4 (TCF4), was required for transcriptional induction of genes encoding anti-apoptotic proteins, contributing to rescuing cardiomyocyte survival. In addition, PCA ameliorated mitochondrial dysfunction and prevented mitochondrial apoptosis dependent on PKM2. Consistently, PCA increased the binding of PKM2 to β-catenin, improved heart contractive function, normalized heart structure and attenuated oxidative damage in mice subjected to artery ligation, but the protective effects were lost in Pkm2-deficient heart. Together, we showed that PCA regulated nuclear PKM2 function to rescue cardiomyocyte survival via β-catenin/TCF4 signaling cascade, suggesting the potential of pharmacological intervention of PKM2 shuttle to protect the heart.
format	article
author	Xunxun Wu Lian Liu Qiuling Zheng Haiping Hao Hui Ye Ping Li Hua Yang
author_facet	Xunxun Wu Lian Liu Qiuling Zheng Haiping Hao Hui Ye Ping Li Hua Yang
author_sort	Xunxun Wu
title	Protocatechuic aldehyde protects cardiomycoytes against ischemic injury via regulation of nuclear pyruvate kinase M2
title_short	Protocatechuic aldehyde protects cardiomycoytes against ischemic injury via regulation of nuclear pyruvate kinase M2
title_full	Protocatechuic aldehyde protects cardiomycoytes against ischemic injury via regulation of nuclear pyruvate kinase M2
title_fullStr	Protocatechuic aldehyde protects cardiomycoytes against ischemic injury via regulation of nuclear pyruvate kinase M2
title_full_unstemmed	Protocatechuic aldehyde protects cardiomycoytes against ischemic injury via regulation of nuclear pyruvate kinase M2
title_sort	protocatechuic aldehyde protects cardiomycoytes against ischemic injury via regulation of nuclear pyruvate kinase m2
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/a57b187724ad48fa880cde6ea6fada65
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Protocatechuic aldehyde protects cardiomycoytes against ischemic injury via regulation of nuclear pyruvate kinase M2

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