Possible regulatory functions of protein kinase C-alpha and -epsilon isoenzymes in rat renal mesangial cells. Stimulation of prostaglandin synthesis and feedback inhibition of angiotensin II-stimulated phosphoinositide hydrolysis.
Short-term treatment of mesangial cells with phorbol 12-myristate 13-acetate (PMA) decreases angiotensin II-induced InsP3 formation, but potentiates hormone-stimulated arachidonic acid release and prostaglandin (PG) E2 synthesis. Long-term treatment with PMA augments hormone-stimulated InsP3 generation (after 8 h treatment), but eliminates angiotensin II-induced arachidonic acid release and PGE2 formation (after 24 h treatment). By using specific antibodies it is observed that mesangial cells express two protein kinase C (PKC) isoenzymes, PKC-alpha and -epsilon. No PKC-beta and -gamma isoenzymes are detected. On exposure to PMA a complete depletion of PKC-alpha is observed within 8 h. In contrast, down-regulation of PKC-epsilon to 10-20% of that found in control cells requires a 24 h treatment with PMA. These results may imply that PKC-alpha mediates feedback inhibition of phosphoinositide hydrolysis, whereas PKC-epsilon is a candidate for regulating PG synthesis in mesangial cells.
Huwiler
A
A
Research Department, Ciba-Geigy Ltd., Basel, Switzerland.
Fabbro
D
D
Pfeilschifter
J
J
D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D005920:Glomerular Mesangium / Q000201:enzymology*; D006868:Hydrolysis; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000502:physiology*; D007700:Kinetics; D008969:Molecular Sequence Data; D010716:Phosphatidylinositols / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007527:Isoenzymes; D010716:Phosphatidylinositols; D000804:Angiotensin II; D016718:Arachidonic Acid; D011493:Protein Kinase C; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate