PMID- 25254904
OWN - NLM
STAT- MEDLINE
DCOM- 20150324
LR  - 20231213
IS  - 1528-1175 (Electronic)
IS  - 0003-3022 (Linking)
VI  - 122
IP  - 1
DP  - 2015 Jan
TI  - Propofol attenuated acute kidney injury after orthotopic liver transplantation 
      via inhibiting gap junction composed of connexin 32.
PG  - 72-86
LID - 10.1097/ALN.0000000000000448 [doi]
AB  - BACKGROUND: Postliver transplantation acute kidney injury (AKI) severely affects 
      patient survival, whereas the mechanism is unclear and effective therapy is 
      lacking. The authors postulated that reperfusion induced enhancement of 
      connexin32 (Cx32) gap junction plays a critical role in mediating postliver 
      transplantation AKI and that pretreatment/precondition with the anesthetic 
      propofol, known to inhibit gap junction, can confer effective protection. 
      METHODS: Male Sprague-Dawley rats underwent autologous orthotopic liver 
      transplantation (AOLT) in the absence or presence of treatments with the 
      selective Cx32 inhibitor, 2-aminoethoxydiphenyl borate or propofol (50 mg/kg) (n 
      = 8 per group). Also, kidney tubular epithelial (NRK-52E) cells were subjected to 
      hypoxia-reoxygenation and the function of Cx32 was manipulated by three distinct 
      mechanisms: cell culture in different density; pretreatment with Cx32 inhibitors 
      or enhancer; Cx32 gene knock-down (n = 4 to 5). RESULTS: AOLT resulted in 
      significant increases of renal Cx32 protein expression and gap junction, which 
      were coincident with increases in oxidative stress and impairment in renal 
      function and tissue injury as compared to sham group. Similarly, 
      hypoxia-reoxygenation resulted in significant cellular injury manifested as 
      reduced cell growth and increased lactate dehydrogenase release, which was 
      significantly attenuated by Cx32 gene knock-down but exacerbated by Cx32 
      enhancement. Propofol inhibited Cx32 function and attenuated post-AOLT AKI. In 
      NRK-52E cells, propofol reduced posthypoxic reactive oxygen species production 
      and attenuated cellular injury, and the cellular protective effects of propofol 
      were reinforced by Cx32 inhibition but cancelled by Cx32 enhancement. CONCLUSION: 
      Cx32 plays a critical role in AOLT-induced AKI and that inhibition of Cx32 
      function may represent a new and major mechanism whereby propofol reduces 
      oxidative stress and subsequently attenuates post-AOLT AKI.
FAU - Luo, Chenfang
AU  - Luo C
AD  - From the Department of Anesthesiology, The Third Affiliated Hospital of Sun 
      Yat-Sen University, Guangzhou, People's Republic of China (C.L., D.Y., X.L., 
      W.Y., G.L., X.C., Z.H.); and Department of Anesthesiology, Li Ka Shing Faculty of 
      Medicine, The University of Hong Kong, Hong Kong, People's Republic of China 
      (H.L., M.G.I., Z.X.).
FAU - Yuan, Dongdong
AU  - Yuan D
FAU - Li, Xiaoyun
AU  - Li X
FAU - Yao, Weifeng
AU  - Yao W
FAU - Luo, Gangjian
AU  - Luo G
FAU - Chi, Xinjin
AU  - Chi X
FAU - Li, Haobo
AU  - Li H
FAU - Irwin, Michael G
AU  - Irwin MG
FAU - Xia, Zhengyuan
AU  - Xia Z
FAU - Hei, Ziqing
AU  - Hei Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Anesthesiology
JT  - Anesthesiology
JID - 1300217
RN  - 0 (Anesthetics, Intravenous)
RN  - 0 (Connexins)
RN  - YI7VU623SF (Propofol)
SB  - IM
MH  - Acute Kidney Injury/genetics/metabolism/*prevention & control
MH  - Anesthetics, Intravenous/metabolism/pharmacology
MH  - Animals
MH  - Blotting, Western/methods
MH  - Cell Culture Techniques
MH  - Cell Survival/drug effects
MH  - Connexins/*drug effects/genetics/metabolism
MH  - Disease Models, Animal
MH  - Gap Junctions/*drug effects/genetics/metabolism
MH  - Gene Expression/drug effects
MH  - Liver/drug effects/metabolism
MH  - Liver Transplantation/*adverse effects/methods
MH  - Male
MH  - Oxidative Stress/drug effects
MH  - Postoperative Complications/genetics/metabolism/*prevention & control
MH  - Propofol/metabolism/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Gap Junction beta-1 Protein
EDAT- 2014/09/26 06:00
MHDA- 2015/03/25 06:00
CRDT- 2014/09/26 06:00
PHST- 2014/09/26 06:00 [entrez]
PHST- 2014/09/26 06:00 [pubmed]
PHST- 2015/03/25 06:00 [medline]
AID - 10.1097/ALN.0000000000000448 [doi]
PST - ppublish
SO  - Anesthesiology. 2015 Jan;122(1):72-86. doi: 10.1097/ALN.0000000000000448.