Universität zu Köln

Li, Zhigang, Zhu, Huifang, Liu, Chang, Wang, Yumei, Wang, Duo, Liu, Huan, Cao, Wenze, Hu, Yi, Lin, Qin, Tong, Chang, Lu, Min, Sachinidis, Agapios, Li, Li and Peng, Luying (2019). GSK-3 beta inhibition protects the rat heart from the lipopolysaccharide-induced inflammation injury via suppressing FOXO3A activity. J. Cell. Mol. Med., 23 (11). S. 7796 - 7810. HOBOKEN: WILEY. ISSN 1582-4934

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Abstract

Sepsis-induced cardiac dysfunction represents a main cause of death in intensive care units. Previous studies have indicated that GSK-3 beta is involved in the modulation of sepsis. However, the signalling details of GSK-3 beta regulation in endotoxin lipopolysaccharide (LPS)-induced septic myocardial dysfunction are still unclear. Here, based on the rat septic myocardial injury model, we found that LPS could induce GSK-3 beta phosphorylation at its active site (Y216) and up-regulate FOXO3A level in primary cardiomyocytes. The FOXO3A expression was significantly reduced by GSK-3 beta inhibitors and further reversed through beta-catenin knock-down. This pharmacological inhibition of GSK-3 beta attenuated the LPS-induced cell injury via mediating beta-catenin signalling, which could be abolished by FOXO3A activation. In vivo, GSK-3 beta suppression consistently improved cardiac function and relieved heart injury induced by LPS. In addition, the increase in inflammatory cytokines in LPS-induced model was also blocked by inhibition of GSK-3 beta, which curbed both ERK and NF-kappa B pathways, and suppressed cardiomyocyte apoptosis via activating the AMP-activated protein kinase (AMPK). Our results demonstrate that GSK-3 beta inhibition attenuates myocardial injury induced by endotoxin that mediates the activation of FOXO3A, which suggests a potential target for the therapy of septic cardiac dysfunction.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Li, Zhigang UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhu, Huifang UNSPECIFIED UNSPECIFIED UNSPECIFIED Liu, Chang UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Yumei UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Duo UNSPECIFIED UNSPECIFIED UNSPECIFIED Liu, Huan UNSPECIFIED UNSPECIFIED UNSPECIFIED Cao, Wenze UNSPECIFIED UNSPECIFIED UNSPECIFIED Hu, Yi UNSPECIFIED UNSPECIFIED UNSPECIFIED Lin, Qin UNSPECIFIED UNSPECIFIED UNSPECIFIED Tong, Chang UNSPECIFIED UNSPECIFIED UNSPECIFIED Lu, Min UNSPECIFIED UNSPECIFIED UNSPECIFIED Sachinidis, Agapios UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Li UNSPECIFIED UNSPECIFIED UNSPECIFIED Peng, Luying UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-141541
DOI:	10.1111/jcmm.14656
Journal or Publication Title:	J. Cell. Mol. Med.
Volume:	23
Number:	11
Page Range:	S. 7796 - 7810
Date:	2019
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1582-4934
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language WNT/BETA-CATENIN; BETA-CATENIN; TRANSCRIPTION FACTORS; MYOCARDIAL DEPRESSION; CARDIAC-HYPERTROPHY; SIGNALING PATHWAY; INDUCED APOPTOSIS; STEM-CELLS; ACTIVATION; AKT Multiple languages Cell Biology; Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14154