Alteration of Nrf2 and p-Nrf2 Protein Expression in Hypokalemic Rat Kidney / 체질인류학회지

ABSTRACT

Potassium (K) balance is regulated not only by ion channels and ion transporters, but also by various genes including NF-E2-related factor 2 (Nrf2). Although mRNA distribution and role of Nrf2 has been studied in hypokalemic kidney, the distribution of Nrf2 and phosphorylated-Nrf2 (p-Nrf2) proteins are not known. The present study was planned to examine the alteration of expression and distribution of Nrf2 and p-Nrf2 protein in the kidney of normal and K-depleted rats using immunohistochemistry. In normal rat kidneys, Nrf2 was highly expressed in the proximal convoluted tubule and proximal straight tubule, moderately in cortical thick ascending limb, and weakly in cortical collecting duct, outer medullary thick ascending limb, and outer medullary collecting duct. In K-depleted groups, the pattern of cellular labeling of Nrf2 protein was identical to that of normal group, but the signal intensity was prominently increased in proximal convoluted tubule and proximal straight tubule especially in rats at K-free diet 3 weeks. In normal rat kidneys, p-Nrf2 was highly expressed in nucleus of cortical thick ascending limb, cortical collecting duct, and glomerular endothelial cell, moderately in distal convoluted tubule and outer medullary collecting duct, and weakly in proximal convoluted tubules and outer medullary thick ascending limb. In K-depleted groups, the pattern of cellular labeling of p-Nrf2 protein was similar to that of normal group, but signal intensity was significantly increased in the nucleus of outer medullary collecting duct from of K-free diet 2 and 3 weeks groups. These results suggest that Nrf2 and p-Nrf2 expression was gradually increased in K-depleted groups of kidney, but Nrf2 and p-Nrf2 expression patterns were not exactly matched. In addition, it is suggested that enhanced expression of Nrf2 and p-Nrf2 in hypokalemic condition may affect the regulation of ion channels and ion transporters and subsequent intracellular signal transduction.