Changes in protein kinase C isoforms in association with vascular hyporeactivity in cirrhotic rat aortas.
OBJECTIVE
Although protein kinase C (PKC) alterations may play a role in the abnormal reactivity of cirrhotic rat aortas, its isoforms and cellular distribution are unknown. We therefore studied the protein expression and cellular distribution of PKC isoforms and their activation in cirrhotic rat aortas.


METHODS
Endothelium-denuded aortas from control and cirrhotic rats were examined. Immunoblots were performed with PKC isoform-specific antibodies. Aortic reactivity was determined for phorbol myristate acetate and phenylephrine after PKC down-regulation.


RESULTS
PKC-alpha expression was reduced in both the cytosolic and membrane fractions in cirrhotic aortas. Trace amounts of PKC-beta were detected in cirrhotic aortas. PKC-delta was detected in the cytosolic fraction of control and cirrhotic aortas. PKC-zeta was detected in the membrane fraction in control aortas and in the cytosolic fraction in cirrhotic aortas. Phorbol myristate acetate and phenylephrine triggered translocation of PKC-alpha and PKC-delta isoforms from the cytosol to the membrane in control aortas; in cirrhotic aortas, only PKC-alpha was translocated. Aortic reactivities were reduced after PKC down-regulation. PKC-alpha and -delta activities were reduced in cirrhotic aortas.


CONCLUSIONS
These results suggest that a change in PKC isoforms may be responsible in part for the abnormal reactivity and intracellular transduction through the PKC pathway in cirrhotic rat aortas.
Tazi
K A
KA
Laboratoire d'Hémodynamique Splanchnique et de Biologie Vasculaire, INSERM Unité 481, Hôpital Beaujon, Clichy, France.
Moreau
R
R
Heller
J
J
Poirel
O
O
Lebrec
D
D
D000818:Animals; D001011:Aorta / Q000503:physiopathology*; D001692:Biological Transport / Q000187:drug effects; D015536:Down-Regulation; D007425:Intracellular Membranes / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014018:Tissue Distribution; D014661:Vasoconstriction / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000503:physiopathology*
D007527:Isoenzymes; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate