Prolonged decrease in hepatic connexin32 in chronic liver injury induced by carbon tetrachloride in rats.
OBJECTIVE
Our previous study indicated that the amount of connexin32, the major gap-junctional protein of rat liver, is transiently reduced in acute liver injury after single administration of hepatotoxic chemicals. This study was designed to examine alteration in the expression of connexin32 in chronic liver injury, unassociated with hepatocyte proliferation.


METHODS
Rats were injected with carbon tetrachloride (CCI4, 0.5 ml/kg) twice a week for 12 weeks. After cessation of CCI4 injection, hepatic contents of connexin32 and its mRNA levels were measured by immunoblotting as well as immunohistochemical examination and by Northern-blot analysis.


RESULTS
The plasma alanine-aminotransferase activity was increased from 30 U/I to about 1000 U/l after 12 weeks of CCI4 injections, but recovered nearly to normal level in 7 days after cessation of the injection. Liver specimens 12 days after the last CCI4 injection appeared cirrhotic with a marked increase in fibrosis. Connexin32 contents in these livers decreased to about 37% of controls. The significant decrease in connexin32 content was sustained for at least 30 days and recovered to the control level by 60 days. The alteration of connexin32 content in chronically injured liver was confirmed immunohistochemically. The level of connexin32-mRNA, however, was not reduced, but rather increased by chronic injection of CCI4.


CONCLUSIONS
The results suggest that intercellular communication is disturbed in chronic liver injury, lasting even after recovery from the acute phase of injury. Since the mRNA levels of connexin32 were sustained, the prolonged decrease in connexin32 contents in these livers might be due to a post-transcriptional change that causes decrease in protein synthesis or a derangement of post-translational controls.
Nakata
Y
Y
Department of Medical Biochemistry, Ehime University School of Medicine, Japan.
Iwai
M
M
Kimura
S
S
Shimazu
T
T
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D015152:Blotting, Northern; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002455:Cell Division; D056486:Chemical and Drug Induced Liver Injury; D002908:Chronic Disease; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D019084:Fluorescent Antibody Technique, Indirect; D015151:Immunoblotting; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097002:Gap Junction beta-1 Protein
D000410:Alanine Transaminase; D002251:Carbon Tetrachloride; D017630:Connexins; D004247:DNA; D012333:RNA, Messenger; D000097002:Gap Junction beta-1 Protein