PMID- 22409254
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20130704
LR  - 20200929
IS  - 1872-034X (Electronic)
IS  - 1386-6346 (Linking)
VI  - 42
IP  - 7
DP  - 2012 Jul
TI  - Role of naofen in apoptosis of hepatocytes induced by lipopolysaccharide through 
      mitochondrial signaling in rats.
PG  - 696-705
LID - 10.1111/j.1872-034X.2012.00972.x [doi]
AB  - 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.
CI  - (c) 2012 The Japan Society of Hepatology.
FAU - Fan, Jun-Hua
AU  - Fan JH
AD  - Department of Gastroenterology, Nagoya University Graduate School of Medicine, 
      Nagoya, Departments of Pharmacology Anesthesiology, Aichi Medical University 
      School of Medicine, Nagakute Health Research Center, Aichi Gakuin University, 
      Nisshin, Aichi Prefecture, Japan.
FAU - Feng, Guo-Gang
AU  - Feng GG
FAU - Huang, Lei
AU  - Huang L
FAU - Tsunekawa, Koji
AU  - Tsunekawa K
FAU - Honda, Takashi
AU  - Honda T
FAU - Katano, Yoshiaki
AU  - Katano Y
FAU - Hirooka, Yoshiki
AU  - Hirooka Y
FAU - Goto, Hidemi
AU  - Goto H
FAU - Kandatsu, Nobuhisa
AU  - Kandatsu N
FAU - Ando, Kazuo
AU  - Ando K
FAU - Fujiwara, Yoshihiro
AU  - Fujiwara Y
FAU - Koide, Tatsuro
AU  - Koide T
FAU - Okada, Shoshiro
AU  - Okada S
FAU - Ishikawa, Naohisa
AU  - Ishikawa N
LA  - eng
PT  - Journal Article
DEP - 20120312
PL  - Netherlands
TA  - Hepatol Res
JT  - Hepatology research : the official journal of the Japan Society of Hepatology
JID - 9711801
EDAT- 2012/03/14 06:00
MHDA- 2012/03/14 06:01
CRDT- 2012/03/14 06:00
PHST- 2012/03/14 06:00 [entrez]
PHST- 2012/03/14 06:00 [pubmed]
PHST- 2012/03/14 06:01 [medline]
AID - 10.1111/j.1872-034X.2012.00972.x [doi]
PST - ppublish
SO  - Hepatol Res. 2012 Jul;42(7):696-705. doi: 10.1111/j.1872-034X.2012.00972.x. Epub 
      2012 Mar 12.