Role of naofen in apoptosis of hepatocytes induced by lipopolysaccharide through mitochondrial signaling in rats

Jun Hua Fan, Guo Gang Feng, Lei Huang, Koji Tsunekawa, Takashi Honda, Yoshiaki Katano, Yoshiki Hirooka, Hidemi Goto, Nobuhisa Kandatsu, Kazuo Ando, Yoshihiro Fujiwara, Tatsuro Koide, Shoshiro Okada, Naohisa Ishikawa

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Aim: Lipopolysaccharide (LPS) causes apoptosis of hepatocytes, which is probably mediated by inflammatory substances released from Kupffer cells (KCs). Recently, we have reported that naofen, a newly found intracellular WD40-repeat protein, has a role in inducing the apoptosis in HEK293 cells. Hence, the present study was undertaken to investigate a role of naofen in the LPS-induced apoptosis of rat hepatocytes. Methods: Rats were treated with i.v. injections of LPS, and livers were extirpated to evaluate expression of naofen and apoptosis. In in vitro experiments, hepatocytes and KCs were separately isolated from rat livers. The incubation medium for KCs treated with LPS (KC-CM) was used for hepatocyte culture. Results: Intravenous injections of LPS enhanced the expression of naofen in the livers. Livers showed terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive staining, and elevated caspase-3 activity. In isolated KCs or hepatocytes, LPS hardly affected naofen expression and caspase-3 activity, whereas incubation of hepatocytes with KC-CM enhanced both naofen expression and caspase-3 activation. Transfection of hepatocyte with naofen siRNA prevented such effects of KC-CM, and clearly eliminated KC-CM-induced reduction of Bcl-2 and Bcl-xL. In contrast, overexpression of naofen in hepatocytes downregulated Bcl-2 and Bcl-xL, released cytochrome c from mitochondria, and activated caspase-3. Conclusion: These results indicate that LPS may induce the hepatic apoptosis in association with enhanced naofen expression, and that naofen may mediate the activation of caspase-3 through downregulating the Bcl-2 and Bcl-xL expression, and releasing cytochrome c from mitochondria to cytoplasm.

Original languageEnglish
Pages (from-to)696-705
Number of pages10
JournalHepatology Research
Volume42
Issue number7
DOIs
Publication statusPublished - 07-2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Infectious Diseases

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