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/reperfusio n, on the expression of connexin 32 (Cx32) was studied. Cx32 is the co mponent 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 mRN A steady-stale levels and the encoding polypeptide from the plasma mem brane within 1 h of reperfusion. In contrast, Cx32 mRNA steady-state l evels were only reduced after 4 h of reperfusion in the nonischemic li ver. This reduction of Cx32 mRNA levels was followed by the disappeara nce of Cx32 on the plasma membrane within 24 h of the insult. Administ ration of actinomycin D prior to the ischemic insult prevented the red uction in Cx32 mRNA in both ischemic and nonischemic liver regions. Pr otein synthesis was blocked during the first hour of reperfusion in th e ischemic liver but not in the nonischemic liver. To mimic this effec t, animals were treated with cycloheximide in absence of the ischemic insult. A reduction in Cx32 mRNA and polypeptide in the liver was obse rved in cycloheximide treated animals. This finding suggests that the decrease in Cx32 expression in the ischemic, but not in the nonischemi c, liver may be due to the inhibition of protein synthesis during isch emia/reperfusion. These observations suggest that an ischemic insult p roduces a selective deteriorating effect on Cx32 expression in both is chemic and nonischemic liver regions probably through different mechan isms.