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Hypokalemia causes metabolic alkalosis and morphological changes of the kidney. K⺠balance is regulated not only by ion channels or pump gene, but also by various genes including NF-E2-related factor 2 (Nrf2). Previous study suggested the possibility that Akt and ERK kinase may be involved in Nrf2 transcriptional gene activation. In present study, we investigate the alterations of Akt, p-Akt, ERK, p-ERK protein in both normal kidney and Kâº-deficient diet kidney using Western blot analysis, and immunohistochemisrty. Our western blot data showed that the expression of Akt and p-Akt was increased gradually in Kâº-depleted diet (from 1W-3W) compared to normal group. The expression of ERK and p-ERK was markedly increased in Kâº-depleted diet 2W in comparison with normal group. Based on our immunostaining results, Akt protein immunoreactivity was prominently increased in outer medullary collecting duct, especially in Kâº-depleted diet 2 weeks. The localization of p-Akt proteins in Kâº-depleted groups was not different from normal group, but the immunoreactivity was significantly increased in distal convoluted tubule, macula densa and outer medullary thick ascending limb in Kâº-depleted diet 1 and 2 weeks groups. ERK protein immunoreactivity was prominently increased in outer medullary collecting duct, especially in Kâº-depleted diet 2 and 3 weeks. The localization of p-ERK proteins in Kâº-depleted groups was not different from normal group, but the immunoreactivity was prominently increased in the nucleus of outer medullary collecting duct especially in Kâº-depleted diet 2 weeks. Taken together, we suggest that the expression of p-Akt was gradually increased in Kâº-depleted groups of kidney, but the expression of p-ERK was markedly increased in Kâº-depleted diet 2 week group. Hence, the promotion of AKT and ERK phosphorylation in hypokalemic condition may be involved in the regulation of ion channels, ion transporters and subsequent intracellular signal transduction.