PMID- 16980044
OWN - NLM
STAT- MEDLINE
DCOM- 20061208
LR  - 20060918
IS  - 0041-1345 (Print)
IS  - 0041-1345 (Linking)
VI  - 38
IP  - 7
DP  - 2006 Sep
TI  - Hypoxia/reoxygenation up-regulated the expression of death receptor 5 and 
      enhanced apoptosis in human hepatocyte line.
PG  - 2207-9
AB  - OBJECTIVES: Ischemia-reperfusion injury (IRI) is a key factor that contributes to 
      early and late dysfunction of liver graft. Although we have known that 
      hepatocytes express death receptors for tumor necrosis factor-related 
      apoptosis-inducing ligand (TRAIL), the effects of TRAIL on hypoxia/reoxygenation 
      (H/R)-mediated apoptosis are unclear. This study sought to examine the effects of 
      H/R on TRAIL cytotoxicity, as a cause of primary hepatic graft dysfunction, 
      delayed graft refunction, and chronic graft dysfunction. METHODS: Using an 
      hepatocyte H/R model in vitro to mimic IRI in the grafted liver, normal human 
      hepatocytes HL-7702 were exposed to hypoxia for 5 hours then reoxygenated for 0, 
      2, 4, 6, or 20 hours. In another experiment, hepatocytes were exposed to hypoxia 
      for 0, 2, 4, 8, or 20 hours. Expressions of TRAIL-R2/Death receptor 5 (DR5) mRNA 
      were measured by semiquantitative reverse-transcriptase polymerase chain 
      reactions. After 16 hours of hypoxia, human hepatocytes were treated with TRAIL 
      in different concentrations for 5 hours. The death of hepatocytes was confirmed 
      by flow cytometer and methyl thiazolyl tetrazolium analysis. RESULT: After 5-hour 
      hypoxia, the expressions of DR5 mRNA increased at all times of reoxygenation. DR5 
      mRNA was up-regulated from 0 hour after reoxygenation, reaching a peak value at 2 
      hours after reoxygenation compared with the normoxia cultured cells. Moreover, 
      DR5 mRNA was up-regulated gradually following prolonged hypoxia. TRAIL-mediated 
      cell killing was concentration-dependent being greater in the hypoxia treatment 
      group compared to the normoxia group. CONCLUSIONS: H/R up-regulated the 
      expression of DR5 and enhanced TRAIL-mediated apoptosis in an human hepatocyte 
      line. The TRAIL pathway might play a critical role in hepatocyte apoptosis 
      induced by IRI.
FAU - Cao, L
AU  - Cao L
AD  - Lab of Transplant Engineering and Immunology, West China Hospital, Sichuan 
      University, Guoxuexiang 37, Chengdu 610041, People's Republic of China.
FAU - Li, Y
AU  - Li Y
FAU - Cheng, F
AU  - Cheng F
FAU - Li, S
AU  - Li S
FAU - Long, D
AU  - Long D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplant Proc
JT  - Transplantation proceedings
JID - 0243532
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFRSF10B protein, human)
SB  - IM
MH  - Apoptosis
MH  - Cell Culture Techniques
MH  - Cell Hypoxia
MH  - Cell Line
MH  - Cell Survival
MH  - Gene Expression Regulation
MH  - Hepatocytes/cytology/*physiology
MH  - Humans
MH  - RNA, Messenger/genetics
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/*genetics
MH  - Reperfusion Injury/physiopathology
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2006/09/19 09:00
MHDA- 2006/12/12 09:00
CRDT- 2006/09/19 09:00
PHST- 2006/09/19 09:00 [pubmed]
PHST- 2006/12/12 09:00 [medline]
PHST- 2006/09/19 09:00 [entrez]
AID - S0041-1345(06)00632-4 [pii]
AID - 10.1016/j.transproceed.2006.06.014 [doi]
PST - ppublish
SO  - Transplant Proc. 2006 Sep;38(7):2207-9. doi: 10.1016/j.transproceed.2006.06.014.