Differential decrease in connexin 32 expression in ischemic and nonischemic regions of rat liver during ischemia/reperfusion.
The effect of a localized hepatic injury, regional ischemia/reperfusion, on the expression of connexin 32 (Cx32) was studied. Cx32 is the component of the major hepatic gap junction. Two regions of the injured liver were analyzed: the area directly affected by the ischemic insult (ischemic liver), and the remainder of the organ (nonischemic liver). In the ischemic liver, there were simultaneous reductions in Cx32 mRNA steady-state levels and the encoding polypeptide from the plasma membrane within 1 h of reperfusion. In contrast, Cx32 mRNA steady-state levels were only reduced after 4 h of reperfusion in the nonischemic liver. This reduction of Cx32 mRNA levels was followed by the disappearance of Cx32 on the plasma membrane within 24 h of the insult. Administration of actinomycin D prior to the ischemic insult prevented the reduction in Cx32 mRNA in both ischemic and nonischemic liver regions. Protein synthesis was blocked during the first hour of reperfusion in the ischemic liver but not in the nonischemic liver. To mimic this effect, animals were treated with cycloheximide in absence of the ischemic insult. A reduction in Cx32 mRNA and polypeptide in the liver was observed in cycloheximide treated animals. This finding suggests that the decrease in Cx32 expression in the ischemic, but not in the nonischemic, liver may be due to the inhibition of protein synthesis during ischemia/reperfusion. These observations suggest that an ischemic insult produces a selective deteriorating effect on Cx32 expression in both ischemic and nonischemic liver regions probably through different mechanisms.
Gingalewski
C
C
Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
De Maio
A
A
D000818:Animals; D017630:Connexins / Q000096:biosynthesis*; D003609:Dactinomycin / Q000494:pharmacology; D007511:Ischemia / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D000097002:Gap Junction beta-1 Protein
D017630:Connexins; D003609:Dactinomycin; D012333:RNA, Messenger; D000097002:Gap Junction beta-1 Protein