PMID- 15808658
OWN - NLM
STAT- MEDLINE
DCOM- 20051028
LR  - 20131121
IS  - 0041-1345 (Print)
IS  - 0041-1345 (Linking)
VI  - 37
IP  - 1
DP  - 2005 Jan-Feb
TI  - 17beta-estradiol differentially activates mitogen-activated protein-kinases and 
      improves survival following reperfusion injury of reduced-size liver in mice.
PG  - 399-403
AB  - Ischemia-reperfusion injury (I/R-I), which is unavoidable in liver 
      transplantation, impairs liver regeneration and predisposes to liver failure. The 
      three major mitogen-activated protein-kinases (MAPKs): ERK, p38, and JNK, are 
      critical in the transmission of signals triggered by proinflammatory cytokines, 
      by stress, and by growth factors. JNK and p38alpha activation have been 
      associated with apoptosis; p38beta with cell survival; and ERK with 
      proliferation. Previous studies have demonstrated gender dimorphism in 
      hepatocellular dysfunction after experimental trauma and hemorrhage. Female mice 
      are protected to a much greater extent from I/R-I than male mice. We assessed the 
      effects of 17beta-estradiol (17beta-E) on liver function, host survival, and 
      cellular activation of MAPK in a murine model of I/R-I in reduced-size livers. 
      C57BL/6 mice were subjected to 45 minutes of warm ischemia (70% of the liver 
      mass). After reperfusion, the nonischemic lobes were excised. Vehicle, 17beta-E 
      or the estrogen receptor antagonist ICI-182780, was delivered 1 hour before the 
      injury. We evaluated AST and apoptosis as well as activation of JNK, p38, and 
      ERK. Female mice showed a lower level of hepatocellular injury (AST = 445 +/- 82 
      IU/L) after I/R-I compared with male mice (AST = 1400 +/- 210). 17beta-E 
      decreased the liver injury in male mice (AST = 522 +/- 77), an effect that was 
      partially reversed by ICI-182,780 (910 +/- 92). A higher rate of apoptosis was 
      observed in male animals given saline (enrichment factor = 7.22 +/- 0.8) versus 
      those treated with 17beta-E (5.85 +/- 0.3, P < .05). A significant increase in 
      liver regeneration, as assessed by the percentage of liver weight/body weight was 
      demonstrated in females (184% +/- 24%) and male mice given 17beta-E (168% +/- 
      22%) compared with male mice given vehicle (9% +/- 4%). 17beta-E significantly 
      down-regulated JNK and p38alpha activities, whereas I/R-I promoted p38beta and 
      ERK activation. These results suggest that the cytoprotective effects of 17beta-E 
      on I/R-I to reduced-size livers are associated with selective modulation of MAPK 
      kinases.
FAU - Vilatoba, M
AU  - Vilatoba M
AD  - Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, 
      USA.
FAU - Eckstein, C
AU  - Eckstein C
FAU - Bilbao, G
AU  - Bilbao G
FAU - Frennete, L
AU  - Frennete L
FAU - Eckhoff, D E
AU  - Eckhoff DE
FAU - Contreras, J L
AU  - Contreras JL
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Transplant Proc
JT  - Transplantation proceedings
JID - 0243532
RN  - 4TI98Z838E (Estradiol)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Enzyme Activation/drug effects
MH  - Estradiol/*pharmacology
MH  - Female
MH  - Liver/drug effects/*enzymology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - *Reperfusion Injury/prevention & control
MH  - Sex Characteristics
EDAT- 2005/04/06 09:00
MHDA- 2005/10/29 09:00
CRDT- 2005/04/06 09:00
PHST- 2005/04/06 09:00 [pubmed]
PHST- 2005/10/29 09:00 [medline]
PHST- 2005/04/06 09:00 [entrez]
AID - S0041-1345(04)01491-5 [pii]
AID - 10.1016/j.transproceed.2004.12.053 [doi]
PST - ppublish
SO  - Transplant Proc. 2005 Jan-Feb;37(1):399-403. doi: 
      10.1016/j.transproceed.2004.12.053.