Effects of Sex Hormones on Na⁺/Glucose Cotransporter of Renal Proximal Tubular Cells following Oxidant Injury

Abstract

It was reported that reactive oxygen metabolites play an important role in the pathogenesis of several renal diseases including glomerulonephritis, ischemia and acute tubular necrosis. However, the effect of oxidants and protective effect of sex steroid hormones on Na⁺/glucose cotransporter of renal proximal tubular cells is not yet elucidated. In the present study, we examined the effect of sex steroid hormones against tert-butyl hydroperoxide (t-BHP)-induced alteration of Na⁺/glucose cotransporter activity in primary cultured rabbit renal proximal tubule cells (PTCs). t-BHP inhibited α-methyl-D-glucopyranoside (α-MG) uptake in a dose-dependent manner. t-BHP-induced inhibition of α-MG uptake was due not to K_m but to the decrease of V_max. 0.5 mM t-BHP-induced inhibition of α-MG uptake was significantly blocked by estradiol-17β, but not by progesterone and testosterone. This protective effect was not blocked by estrogen receptor antagonist or transcription and translation inhibitor. In addition, 0.5 mM t-BHP increased [³H]-arachidonic acid (AA) release and Ca²⁺ uptake. These effects of t-BHP were also significantly blocked by estradiol-17β, but not by progesterone and testosterone. Protective efficacy of estradiol-17β on t-BHP-induced inhibition of α-MG uptake is exhibited between antioxidants and iron chelators. In conclusion, estradiol-17β, but not progesterone and testosterone, partially prevented t-BHP-induced inhibition of α-MG uptake through its antioxidant activity dependent upon phenol structures and inhibition of AA release and Ca²⁺ influx.

Ginsenosides Protect Apical Transporters of Cultured Proximal Tubule Cells from Dysfunctions Induced by H₂O₂

“…It is proposed that PTCs are very susceptible to oxidative stress [20] and the tubulointerstitial cells following H 2 O 2 exposure represent a spectrum of alterations in renal function [21]. One of the most common renal PTC changes in response to oxidative stress may be alteration in transport functions [12,13]. The specificity of apical transporters was not shown in this study, since H 2 O 2 inhibited ·-MG, Pi, and Na + uptake.…”

“…Na + -dependent glucose transport, a hallmark of proximal tubule function, has the same properties in culture as the tissue in vivo. Therefore, primary cultured renal proximal tubule cells (PTCs) in serum-free and hormonally defined culture conditions can be used to study the effect of ginsenosides on transporter activity of kidney proximal tubules [12,13]. Many studies have used H 2 O 2 as a model agent to study the mechanisms of cell injury resulting from acute oxidative stress in various cells and tissues [2,3].…”

Oxalate inhibits renal proximal tubule cell proliferation via oxidative stress, p38 MAPK/JNK, and cPLA2 signaling pathways

“…The primary rabbit renal PTC culture system that was utilized in this study is well recognized to retain in vitro the differentiated phenotype typical of the renal proximal tubule, including a polarized morphology (38), apical membrane proteins (leucine aminopeptidase and ␥-glutamyltranspeptidase), distinctive proximal tubule transport systems including the Na ϩ -glucose cotransport system (21), as well as hormone responses (20). The primary rabbit renal PTC culture system that was utilized in this study is well recognized to retain in vitro the differentiated phenotype typical of the renal proximal tubule, including a polarized morphology (38), apical membrane proteins (leucine aminopeptidase and ␥-glutamyltranspeptidase), distinctive proximal tubule transport systems including the Na ϩ -glucose cotransport system (21), as well as hormone responses (20).…”

Neuroimmunoendocrine Link Between Chronic Kidney Disease and Olfactory Deficits

“…It is not surprising that sex hormones influence kidney function since androgen, estrogen, and progesterone receptors exist in this organ ( Davidoff et al, 1980 ; Takeda et al, 1990 ; Bhat et al, 1993 ; Han et al, 2001 ; Sabolic et al, 2007 ). In humans, sex hormones are also produced within the kidney, raising the possibility of autocrine and paracrine regulation of renal functions ( Sharpe, 1998 ; Quinkler et al, 2003 ).…”