Effect of EGF on H2O2-induced inhibition of alpha-MG uptake in renal proximal tubule cells: involvement of MAPK and AA release

Journal of Cellular Physiology
Ho Jae HanMary Taub

Abstract

Both oxidative stress and epidermal growth factor (EGF) contribute to the initiation and progression of renal proximal tubular dysfunction under pathophysiologic conditions. Thus, this study was performed (1) to examine both the individual, and the combined effects of H2O2 and EGF on alpha-methyl-D-glucopyranoside uptake (alpha-MG uptake) in the primary cultured renal proximal tubule cells (PTCs), and (2) to elucidate the involvement of p44/42 mitogen activated protein kinase (MAPK) and phospholipase A2 in mediating these actions. Both H2O2 and EGF inhibited alpha-MG uptake individually, while the combination of H2O2 and EGF further potentiated the inhibitory effect on alpha-MG uptake, which was elicited by each agent. H2O2 not only caused a rapid increase in the phosphorylation of p44/42 MAPK, but also promoted the translocation of cytosolic phospholipase A2 (cPLA2) from the cytosolic to particulate fraction, and stimulated cellular [3H]-arachidonic acid (AA) release. EGF similarly activates phosphorylation of p44/42 MAPK and stimulates [3H]-AA release. When PTCs were exposed to 100 microM H2O2 and 50 ng/ml EGF simultaneously, a further increase in the phosphorylation of p44/42 MAPK, of [3H]-AA release, and of prostaglandin E2...Continue Reading

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Citations

Aug 4, 2007·Kidney International. Supplement·Y J LeeH J Han
Mar 1, 2012·The Journal of Pharmacology and Experimental Therapeutics·Christina L JonesElizabeth A Cowley
Aug 19, 2007·American Journal of Physiology. Renal Physiology·Sunhapas SoodvilaiTianxin Yang
Jun 22, 2007·American Journal of Physiology. Renal Physiology·Yu Jin LeeHo Jae Han

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