AGEs induce oxidative stress and activate protein kinase C-βIIin neonatal mesangial cells
| Autor: | Michael B. Ganz, Miriam F. Weiss, Vincenzo Scivittaro |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Glycation End Products
Advanced medicine.medical_specialty Physiology Renal glomerulus Protein Kinase C beta Biology Rats Sprague-Dawley chemistry.chemical_compound Glycation Internal medicine medicine Animals Cells Cultured Protein Kinase C Protein kinase C Mesangial cell Kinase Biological Transport Intracellular Membranes Glomerular Mesangium Rats Cell biology Enzyme Activation Isoenzymes Oxidative Stress Endocrinology Animals Newborn chemistry Advanced glycation end-product Cell Division Intracellular |
| Zdroj: | American Journal of Physiology-Renal Physiology. 278:F676-F683 |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.2000.278.4.f676 |
| Popis: | 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. Blocking PKC-βIIhas been shown to decrease albuminuria in animal models of diabetes. To demonstrate a direct relationship between AGEs and the induction and translocation of PKC-βII, studies were carried out in rat neonatal mesangial cells, known to express PKC-βIIin association with rapid proliferation in post-natal development. Oxidative stress was studied by using the fluorescent probe dichlorfluorescein diacetate. Translocation of PKC-βIIwas 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-βIItranslocation (with no change in PKC-α) were demonstrated after exposure to AGE-rich proteins. These data support the hypothesis that AGEs cause mesangial oxidative stress and alterations in PKC-βII, changes that may ultimately contribute to phenotypic abnormalities associated with diabetic nephropathy. |
| Databáze: | OpenAIRE |
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