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ChemicalBook >> journal list >> Cell Death and Differentiation >>article
Cell Death and Differentiation

Cell Death and Differentiation

IF: 15.4
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Histone methyltransferase G9a protects against acute liver injury through GSTP1

Published:12 September 2019 DOI: 10.1038/s41418-019-0412-8
Yu Zhang, Weili Xue, Wenquan Zhang, Yangmian Yuan, Xiuqin Zhu, Qing Wang, Yujuan Wei, Dong Yang, Chen Yang, Yan Chen, Yu Sun, Shun Wang, Kun Huang, Ling Zheng

Abstract

Acute liver injury is commonly caused by bacterial endotoxin/lipopolysaccharide (LPS), and by drug overdose such as acetaminophen (APAP). The exact role of epigenetic modification in acute liver injury remains elusive. Here, we investigated the role of histone methyltransferase G9a in LPS- or APAP overdose-induced acute liver injury. Under d-galactosamine sensitization, liver-specific G9a-deficient mice (L-G9a?/?) exhibited 100% mortality after LPS injection, while the control and L-G9a+/? littermates showed very mild mortality. Moreover, abrogation of hepatic G9a or inhibiting the methyltransferase activity of G9a aggravated LPS-induced liver damage. Similarly, under sublethal APAP overdose, L-G9a?/? mice displayed more severe liver injury. Mechanistically, ablation of G9a inhibited H3K9me1 levels at the promoters of Gstp1/2, two liver detoxifying enzymes, and consequently suppressed their transcription. Notably, treating L-G9a?/? mice with recombinant mouse GSTP1 reversed the LPS- or APAP overdose-induced liver damage. Taken together, we identify a novel beneficial role of G9a-GSTP1 axis in protecting against acute liver injury.

Substances (16)

Materials
Procduct Name CAS Molecular Formula Supplier Price
beta-Cyclodextrin methyl ethers 128446-36-6 C54H94O35 430 suppliers $5.00-$14610.00
beta-Cyclodextrin methyl ethers 128446-36-6 C54H94O35 430 suppliers $5.00-$14610.00
beta-Cyclodextrin methyl ethers 128446-36-6 C54H94O35 430 suppliers $5.00-$14610.00
beta-Cyclodextrin methyl ethers 128446-36-6 C54H94O35 430 suppliers $5.00-$14610.00
Dynasore 304448-55-3 C18H14N2O4 185 suppliers $12.00-$2755.00
Dynasore 304448-55-3 C18H14N2O4 185 suppliers $12.00-$2755.00
Dynasore 304448-55-3 C18H14N2O4 185 suppliers $12.00-$2755.00
Dynasore 304448-55-3 C18H14N2O4 185 suppliers $12.00-$2755.00
BIX 01294 1392399-03-9 C28H41Cl3N6O2 102 suppliers $15.00-$2112.00
BIX 01294 1392399-03-9 C28H41Cl3N6O2 102 suppliers $15.00-$2112.00

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