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World J Gastroenterol. May 7, 2014; 20(17): 4963-4971
Published online May 7, 2014. doi: 10.3748/wjg.v20.i17.4963
Published online May 7, 2014. doi: 10.3748/wjg.v20.i17.4963
Naofen promotes TNF-α-mediated apoptosis of hepatocytes by activating caspase-3 in lipopolysaccharide-treated rats
Jun-Hua Fan, Guo-Duo Tang, Hai-Xing Jiang, Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Guo-Gang Feng, Lei Huang, Department of Pharmacology, Aichi Medical University School of Medicine, Nagakute, Aichi-gun 480-1195, Japan
Jing Xu, Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Author contributions: Fan JH, Feng GG and Huang L performed the majority of experiments; Tang GG, Jiang HX and Xu J analyzed the data; Fan JH and Feng GG designed the study and wrote the paper.
Correspondence to: Jun-Hua Fan, MD, PhD, Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China. fanjunhuaxiaoshe@hotmail.com
Telephone: +86-771-5356501 Fax: +86-771-5356585
Received: October 25, 2013
Revised: December 25, 2013
Accepted: March 5, 2014
Published online: May 7, 2014
Revised: December 25, 2013
Accepted: March 5, 2014
Published online: May 7, 2014
Core Tip
Core tip: Naofen, a WD40-repeat protein, is increased in the liver but not in the kidneys, thymus or spleen of rats injected with lipopolysaccharide (LPS). Increased naofen expression is blocked by pretreatment with anti-tumor necrosis factor (TNF)-α antibody. TNF-α has no effect on naofen expression or caspase-3 activation in primary hepatocytes, but conditioned medium from LPS-treated Kupffer cells (KC-CM) significantly enhances both. KC-CM-induced increase in naofen expression and caspase-3 activity is blocked by anti-TNF-α antibody. LPS in the liver may enhance release of TNF-α from KCs, and induce hepatocyte apoptosis, for which naofen promotes caspase-3 activity through the mitochondrial pathway.