ETHANOL CAUSES TRANSLOCATION OF CAMP-DEPENDENT PROTEIN-KINASE CATALYTIC SUBUNIT TO THE NUCLEUS

Short- and long-term ethanol exposures have been shown to alter cellul ar levels of cAMP, but little is known about the effects of ethanol on cAMP-dependent protein kinase (PKA), When cAMP levels increase, the c atalytic subunit of PKA (C alpha) is released from the regulatory subu nit, phosphorylates nearby proteins, and then translocates to the nucl eus, where it regulates gene expression. Altered localization of C alp ha would have profound effects on multiple cellular functions. Therefo re, we investigated whether ethanol alters intracellular localization of C alpha. NG108-15 cells were incubated in the presence or absence o f ethanol for as long as 48 h, and localization of PKA subunits was de termined by immunocytochemistry. We found that ethanol exposure produc ed a significant translocation of C alpha from the Golgi area to the n ucleus. C alpha remained in the nucleus as long as ethanol was present . There was no effect of ethanol on localization of the type I regulat ory subunit of PKA. Ethanol also caused a 43% decrease in the amount o f type I regulatory subunit but had no effect on the amount of C alpha as determined by Western blot, These data suggest that ethanol-induce d translocation of C alpha to the nucleus may account, in part, for di verse changes in cellular function and gene expression produced by alc ohol.