Estradiol protects against alteration of protein kinase Cɛ in a binge model of ethanol dependence and withdrawal

This study tested the hypothesis that a binge type of ethanol intake and ethanol withdrawal disturbs protein kinase C (PKC) homeostasis in a manner protected by 17β-estradiol. Ovariectomized rats implanted with 17β-estradiol or oil pellets received ethanol (7.5% weight/volume, 7 days) or control solution by a gavage method. The cerebelli were collected during ethanol exposure or ethanol withdrawal to assess the activity, protein levels, and cellular distribution of PKCɛ and total PKC, using an ATP phosphorylation and immunoblot assays. While both ethanol exposure and ethanol withdrawal increased membrane protein levels and membrane translocation, only ethanol withdrawal enhanced activity of PKCɛ. Ethanol withdrawal not ethanol exposure increased the three parameters of total PKC. 17β-Estradiol treatment prevented these changes in PKC profiles. These data suggest that an excessive episodic intake of ethanol followed by ethanol withdrawal disturbs PKC homeostasis and cellular distribution of PKC, in particular PKCɛ, in a manner that is protected by estrogen. PKCɛ appears more vulnerable during ethanol withdrawal than during ethanol exposure.