TY - JOUR
T1 - Overexpression of protein kinase C-ζ isoform increases cyclooxygenase- 2 and inducible nitric oxide synthase
AU - Miller, Brent W.
AU - Baier, Lisa D.
AU - Morrison, Aubrey R.
PY - 1997/7
Y1 - 1997/7
N2 - 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 ζ-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-ζ showed no change in morphology, PGE2 production, COX- 2 expression, or iNOS expression at basal conditions. This suggests a role for PKC-ζ in the expression of these enzymes in mesangial cells.
AB - 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 ζ-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-ζ showed no change in morphology, PGE2 production, COX- 2 expression, or iNOS expression at basal conditions. This suggests a role for PKC-ζ in the expression of these enzymes in mesangial cells.
KW - Arachidonic acid
KW - Inflammation
KW - Mesangial cells
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=0030794991&partnerID=8YFLogxK
U2 - 10.1152/ajpcell.1997.273.1.c130
DO - 10.1152/ajpcell.1997.273.1.c130
M3 - Article
C2 - 9252450
AN - SCOPUS:0030794991
SN - 0363-6143
VL - 273
SP - C130-C136
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
IS - 1 42-1
ER -