Gene expression profiles of sodium-dependent vitamin C transporters in mice after alcohol consumption

Abstract

Alcoholic liver disease (ALD) is a serious liver problem in western countries. Our previous study has demonstrated that vitamin C plays a protective role in ALD. The vitamin C homeostasis is tightly regulated by sodium-dependent vitamin C transporters (SVCTs) 1 and 2. But the role of two SVCTs in ALD is less understood. In this study, we examined the expression patterns of two SVCTs in mice after alcohol consumption. Our results suggested that alcohol consumption obviously increased the expression of two SVCTs in liver and SVCT1 in kidney and intestine, which is important for vitamin C absorption. Vitamin C supplement increased the sera vitamin C content and ameliorated the symptom of ALD. Intestinal absorption and renal re-absorption mediated by SVCT1 are key factors to increase the sera vitamin C content after alcohol consumption. We proposed that both reactive oxygen species and low vitamin C concentration regulate the expression of SVCTs, and the protective role of vitamin C is mediated by suppressing the stability of hypoxia-inducible factor-1a. Thus, our study is significant for the understanding of vitamin C homeostasis in ALD and for better use of other antioxidants in ALD therapy.

Analysis of membrane transport mechanisms of endogenous substrates using chromatographic techniques

“…SLC19A1/RFC, SLC46A1/PCFT and ABCC2 were determined to contribute to the transport of folate in Caco‐2 cells using a transport buffer assay with separation on a C 18 column and detection by UV absorptiometry at 280 nm (Yan et al, ). SLC23A1/SVCT1 and SLC23A2/SVCT2 were shown to function as ascorbate transporters via the analysis of plasma, serum, aqueous humor and lens nucleolus samples from humans as well as serum and liver homogenates from mice (Cahill & El‐Sohemy, ; Guo et al, ; Senthilkumari et al, ). Guo et al demonstrated the increased serum ascorbate level in mice after alchohol consumption (Guo et al, ).…”

“…SLC23A1/SVCT1 and SLC23A2/SVCT2 were shown to function as ascorbate transporters via the analysis of plasma, serum, aqueous humor and lens nucleolus samples from humans as well as serum and liver homogenates from mice (Cahill & El‐Sohemy, ; Guo et al, ; Senthilkumari et al, ). Guo et al demonstrated the increased serum ascorbate level in mice after alchohol consumption (Guo et al, ). The authors suggested that the expression levels of two SVCTs in liver and SVCT1 in kidney and intestine, which is important for vitamin C absorption, were increased by alchohol consumption.…”

Role of HIF-1α in Alcohol-Mediated Multiple Organ Dysfunction

“…The liver is the primary organ of alcohol metabolism [8]. Clinical and animal models of alcohol exposure show elevations in plasma alanine aminotransferase (ALT) and/or lipopolysaccharides (LPS)/endotoxin levels [55,56,57,58,59,60,61,62,63,64,65,66,67]. Alcohol feeding increases liver steatosis, lipid peroxidation, and/or hepatic damage [55,56,57,58,59,61,63,64,66,68,69,70,71,72].…”

“…The relationship between HIF-1α and alcohol consumption has been widely examined in the liver. Both binge and chronic alcohol consumption elevated HIF-1α in the liver [55,58,59,60,61,62,63,64,66,67,68,70,71,72], including in endothelial cells [73,74,76] and Kupffer cells [77]. Mice with hepatocyte-specific knockout of HIF-1α demonstrate reduced inflammation, steatosis, and serum ALT following chronic alcohol feeding [61,66].…”

“…RES significantly diminished liver fat deposition, serum ALT and aspartate aminotransferase (AST), liver HIF-1α protein levels, and mitochondrial ROS production in ethanol-fed rats [64]. Vitamin C is another antioxidant that has been shown to have protective effects against alcoholic liver disease by suppressing HIF-1α stabilization [62]. Similarly, treatment with the mitochondria-target antioxidant ubiquinone (MitoQ) reduced alcohol-induced HIF-1α expression, hepatic steatosis, lipid peroxidation, and protein nitration in rats [70].…”