Differential decrease in Connexin 32 expression in ischemic and nonischemic regions of rat liver during ischemia/reperfusion

Abstract

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.

Gap junctions and non-neoplastic liver disease

“…Identical changes were seen in concentration of calcium, which is known to move intercellularly through gap junctions [66]. In a similar experimental model, it was found that the reductions in Cx32 mRNA and protein amounts occur at different time points and are driven by different posttranscriptional and posttranslational mechanisms in ischemic and non-ischemic liver areas during reperfusion [67]. In addition to a pronounced inflammatory response, a major factor that contributes to ischemia and reperfusion injury includes the generation of oxygen-derived free radicals [62][63][64].…”

Inflammatory conditions induce gap junctional communication between rat Kupffer cells both in vivo and in vitro

“…Cx32 and Cx26, two parenchymal cells Cxs, are reduced in acute liver inflammation induced by LPS (5,(23)(24)(25)(26), hepatic ischemia/ reperfusion (25), and cholestasis caused by common bile duct ligation (5,27). Under these conditions the expression of Cx43 by KCs, non-parenchymal cells, is enhanced to clear/repair the damage.…”

Downregulation of connexin32 protein and gap-junctional intercellular communication by cytokine-mediated acute-phase response in immortalized mouse hepatocytes

“…The expression of Cx32 has been reported to be posttranscriptionally downregulated in rat liver because of a decreased stability of Cx32 mRNA (Gingalewski et al 1996). More recently, Gingalewski and De Maio (1997) have shown that, in addition to the decreased level of Cx32 mRNA, the level of Cx32 protein is decreased in ischemic rat liver.…”