LIPOPOLYSACCHARIDE-RESPONSIVE PROTEIN-KINASE-C ISOTYPES IN THE ADULT-RAT AORTA

Previous studies have shown that protein kinase C (PKC) activity incre ases in cardiovascular tissue exposed to lipopolysaccharide (LPS). The objective of these experiments was to identify the PKC isotypes that respond to LPS treatment in the adult rat aorta. We found that PKC alp ha, -delta, -epsilon, and -zeta isotypes are present in endothelium-in tact aortas. The PKC alpha and -epsilon isotypes show two- to threefol d increases in abundance after 3 h treatment with 100 ng/mL LPS, while PKC delta and -zeta levels do not increase. In contrast, mRNA for all of the PKC isotypes increased 3.5 to 12-fold during LPS treatment. Bo th PKC isotype and mRNA levels gradually diminished during 20 h of con tinuous LPS exposure. Concurrent treatment of the vessels with LPS plu s 50 mu M cycloheximide caused PKC alpha, -epsilon, and -zeta, but not -delta, isotypes to rapidly decrease in abundance while blunting the increase in PKC isotype mRNA. The major source for all of the PKC isot ypes in the vessel is the vascular smooth muscle cells. These results indicate that LPS treatment induces time-dependent increases in PKC is otype mRNA expression and isotype-specific PKC activation and synthesi s in vascular tissue.