作者
Takuya Seike, Piyakarn Boontem, Masahiro Yanagi, Shihui Li, Hidenori Kido, Daisuke Yamamiya, Hidetoshi Nakagawa, Hikari Okada, Tatsuya Yamashita, Kenichi Harada, Mitsuru Kikuchi, Yoshitake Shiraishi, Noriyuki Ozaki, Shuichi Kaneko, Tetsumori Yamashima, Eishiro Mizukoshi
发表日期
2022/1/1
期刊
Cellular and Molecular Gastroenterology and Hepatology
卷号
14
期号
4
页码范围
925-944
出版商
Elsevier
简介
Background & Aims
The lipid oxidation is a key factor for damaging hepatocytes and causing cell death. However, the mechanisms underlying hepatocyte death and the role of the most popular lipid peroxidation product 4-hydroxy-2-nonenal (HNE) in nonalcoholic steatohepatitis (NASH) remains unclear.
Methods
We demonstrated using hepatoma cell lines, a NASH mouse model, HNE-treated monkeys, and biopsy specimens from patients with NASH that HNE induced hepatocyte death by disintegrating the lysosomal limiting membrane.
Results
The degree of HNE deposition in human NASH hepatocytes was more severe in cases with high lobular inflammation, ballooning, and fibrosis scores, and was associated with enlargement of the staining of lysosomes in hepatocytes. In in vitro experiments, HNE activated μ-calpain via G-protein coupled receptor (GPR) 120. The resultant rupture/permeabilization of the …
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T Seike, P Boontem, M Yanagi, S Li, H Kido… - Cellular and Molecular Gastroenterology and …, 2022