Overexpression of protein kinase C-zeta isoform increases cyclooxygenase-2 and inducible nitric oxide synthase

Abstract

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.

Acid- and bile-induced PGE2release and hyperproliferation in Barrett's esophagus are COX-2 and PKC-ε dependent

“…Work from our laboratory (33) and others (22,23,36) provides evidence that COX-2 is important for the genesis of cancer. Hence there is evidence to link the activity of PKC to carcinogenesis, in part via the induction of COX-2 and overproduction of prostaglandins.…”

Overexpression of atypical PKC in PC12 cells enhances NGF-responsiveness and survival through an NF-κB dependent pathway

“…38 Overexpression of PKC-z in rat mesangial cells enhanced COX-2 expression and inducible nitric oxide synthase. 39 PKC-i overexpression has been shown to protect cells from UV-induced cell death, 40 as well as, okadaic acid-and taxol-induced apoptosis. 37 Moreover, overexpression of atypical PKC in NIH3T3 cells has been shown to block PAR4-induced apoptosis.…”

Interleukin-1β-induced Cyclooxygenase-2 Expression Requires Activation of Both c-Jun NH2-terminal Kinase and p38 MAPK Signal Pathways in Rat Renal Mesangial Cells

“…1-24 h later the culture supernatant was removed and filtered through a 0.45-m membrane (Gelman Sciences) and diluted 1:3 with mesangial medium. Hexadimethrine bromide (Polybrene) was then added to a final concentration of 8 g/ml (18). Primary rat mesangial cells were cultured as described previously (17).…”