Signalling pathways involved in retinal endothelial cell proliferation induced by advanced glycation end products: inhibitory effect of gliclazide

Abstract

Our results demonstrate the involvement of PKC, MAPK and NF-kappaB in AGE-induced BREC proliferation and VEGF expression. Gliclazide inhibits BREC proliferation by interfering with these intracellular signal transduction pathways.

Effect of vitamin E and C supplementation combined with oral antidiabetic therapy on the endothelial dysfunction in the neonatally streptozotocin injected diabetic rat

“…It has also recently been reported that both gliclazide and antioxidants, such as vitamin E or N-acetyl-L-cysteine, inhibit the activation of intracellular signal transduction pathways (i.e. protein kinase C, mitogen-activated protein kinase or nuclear factor-κB) by advanced glycation endproducts (AGE) in cultured retinal endothelial cells, thereby prevent AGE-induced cell proliferation [42]. Therefore, it is rational to combine any antioxidant to gliclazide treatment in order to potentiate its therapeutic effect.…”

Plasma advanced glycation endproduct, methylglyoxal-derived hydroimidazolone is elevated in young, complication-free patients with Type 1 diabetes

“…RAGE is expressed on the surface of a variety of cell types, including endothelial cell, smooth muscle cells, mononuclear phagocytes, neurons, cardiac myocytes, and hepatocytes [31]. AGE binding to RAGE results in activation of several intracellular signaling pathways [32][33][34]. This promotes an increase in oxidative stress and the generation of proinflammatory and prosclerotic cytokines, leading to the disturbances in cellular function that may result in diabetic complications [34][35][36].…”

Effect of Nitric Oxide-cGMP-Dependent Protein Kinase Activation on Advanced Glycation End-Product–Induced Proliferation in Renal Fibroblasts

“…Consistent with the results from the phosphorylation assays, treatment with SNAP, SNP, and 8-pCPT-cGMP inhibited AGE-enhanced STAT5 protein-DNA binding activities. On the other hand, recent studies have indicated that activation of the MAPK pathway is associated with AGE-increased cell proliferation (36,37). Therefore, we also examined whether NO-PKG regulates p42/p44 MAPK activity in NRK-49F cells treated with AGE.…”