AGEs induce oxidative stress and activate protein kinase C-βII in neonatal mesangial cells

Vincenzo Scivittaro, Michael B. Ganz, Miriam F. Weiss
2000 AJP - Renal Physiology  
Scivittaro, Vincenzo, Michael B. Ganz, and Miriam F. Weiss. AGEs induce oxidative stress and activate protein kinase C-␤ II in neonatal mesangial cells. Am J Physiol Renal Physiol 278: F676-F683, 2000.-Increased activation of specific protein kinase C (PKC) isoforms and increased nonenzymatic glycation of intracellular and extracellular proteins [the accumulation of advanced glycation end products (AGEs)] are major mechanistic pathways implicated in the pathogenesis of diabetic complications.
more » ... ocking PKC-␤ II has been shown to decrease albuminuria in animal models of diabetes. To demonstrate a direct relationship between AGEs and the induction and translocation of PKC-␤ II , studies were carried out in rat neonatal mesangial cells, known to express PKC-␤ II in association with rapid proliferation in post-natal development. Oxidative stress was studied by using the fluorescent probe dichlorfluorescein diacetate. Translocation of PKC-␤ II was demonstrated by using immunofluorescence and Western blotting of fractionated mesangial cells. Induction of intracellular oxidative stress, increase in intracellular calcium, and cytosol to membrane PKC-␤ II translocation (with no change in PKC-␣) were demonstrated after exposure to AGE-rich proteins. These data support the hypothesis that AGEs cause mesangial oxidative stress and alterations in PKC-␤ II , changes that may ultimately contribute to phenotypic abnormalities associated with diabetic nephropathy.
doi:10.1152/ajprenal.2000.278.4.f676 pmid:10751230 fatcat:thzkbrahgfg5tbsxrlvytg52ty