Overexpression of protein kinase C-zeta isoform increases cyclooxygenase-2 and inducible nitric oxide synthase.
Cyclooxygenase (COX) catalyzes the formation of prostaglandins from arachidonic acid. Nitric oxide synthase catalyzes the production of nitric oxide, a short-lived messenger molecule involved in many diverse cellular processes. Both of these enzymes have inducible forms [COX-2 and inducible nitric oxide synthase (iNOS), respectively] that respond to environmental stresses, chemicals, and extracellular ligands such as interleukin-1, epidermal growth factor, and platelet-derived growth factor. The precise cascade of intracellular events that leads to the expression of either COX-2 or iNOS is not known. Protein kinase C (PKC) is a family of 11 serine-threonine kinases conserved throughout eukaryotic species that transduce a wide variety of signals critical for cellular functions. Using a retroviral vector to overexpress the zeta-isoform of PKC in rat mesangial cells, we demonstrate markedly increased COX-2, prostaglandin E2 (PGE2), iNOS, and altered cellular morphology compared with mesangial cells expressing a control retroviral vector and untransfected mesangial cells. NIH/3T3 cells overexpressing PKC-zeta showed no change in morphology, PGE2 production, COX-2 expression, or iNOS expression at basal conditions. This suggests a role for PKC-zeta in the expression of these enzymes in mesangial cells.
Miller
B W
BW
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Baier
L D
LD
Morrison
A R
AR
D016475:3T3 Cells; D000818:Animals; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004790:Enzyme Induction; D005822:Genetic Vectors; D005920:Glomerular Mesangium / Q000166:cytology* / Q000378:metabolism*; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000096:biosynthesis; D012190:Retroviridae; D014162:Transfection; D000099221:Protein Kinase C zeta
D051546:Cyclooxygenase 2; D015232:Dinoprostone; D007527:Isoenzymes; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D011493:Protein Kinase C; D011994:Recombinant Proteins; D000099221:Protein Kinase C zeta