Autophagy is involved in the protective effect of p21 on LPS-induced cardiac dysfunction.

Cell Death & Disease
Sihui HuangQizhu Tang

Abstract

p21 has emerged as an important protein involved in cardiovascular diseases, but its role remains controversial. Recently, p21 has been reported to mediate inflammatory responses. As inflammatory responses are a feature of sepsis, our study investigated whether p21 has a role in cardiac dysfunction induced by sepsis and analyzed the mechanisms involved. To establish a mouse sepsis model, p21 global knockout (p21KO) and C57BL/6J wild-type (WT) male mice were treated with 5 mg/kg LPS intraperitoneally for 6, 24, or 48 h. After LPS stimulation, the level of p21 had significantly increased in the WT mice and in cardiomyocytes. Cardiac dysfunction induced by LPS was markedly aggravated in p21KO mice relative to that of WT mice. Downregulation of p21 expression exacerbated the LPS-mediated inflammatory response, and it increased oxidative stress as well as mitochondrial damage in the heart and in cardiomyocytes. In contrast, overexpressing p21 attenuated the increase of TNFα and promoted the increase of SOD2. Moreover, p21 regulated the LPS-induced autophagy activation; that is, the increase in autophagy was impaired when p21 expression was decreased, whereas the increase was significant when p21 was overexpressed. The autophagy indu...Continue Reading

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Citations

Mar 11, 2021·American Journal of Physiology. Cell Physiology·Leena P Bharath, Barbara S Nikolajczyk
May 28, 2021·Frontiers in Cardiovascular Medicine·Jiawen LiYifei Li
Aug 28, 2021·International Journal of Molecular Sciences·Akhilesh KumarRuth K Globus

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Methods Mentioned

BETA
MDA
electron microscopy
CoIP
PCR
transfection
electrophoresis
Assay
Fluorescence

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