Estradiol protects against alteration of protein kinase C(epsilon) 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 17beta-estradiol. Ovariectomized rats implanted with 17beta-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 PKC(epsilon) 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 PKC(epsilon). Ethanol withdrawal not ethanol exposure increased the three parameters of total PKC. 17beta-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 PKC(epsilon), in a manner that is protected by estrogen. PKC(epsilon) appears more vulnerable during ethanol withdrawal than during ethanol exposure.
Jung
Marianna Eunsun
ME
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd., Fort Worth, TX 76107-2699, USA. mjung@hsc.unt.edu
Jacobs
Stephanie
S
Rewal
Mridula
M
Wilson
Andrew
A
Simpkins
James William
JW
D000435:Alcoholic Intoxication / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology* / Q000627:therapeutic use; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D005260:Female; D015151:Immunoblotting; D010052:Ovariectomy; D011493:Protein Kinase C / Q000378:metabolism*; D051744:Protein Kinase C-epsilon; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000201:enzymology* / Q000517:prevention & control
D000431:Ethanol; D004958:Estradiol; C497257:Prkce protein, rat; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon