Slc25a39 and Slc25a40 Expression in Mice with Bile Duct Ligation or Lipopolysaccharide Treatment

Abstract

SLC25A39/40, involved in mitochondrial GSH (mGSH) import from the cytoplasm, is essential for protection against oxidative stress and mitochondrial dysfunction. We examined the effects of cholestasis, through bile duct ligation (BDL) and lipopolysaccharide (LPS)-induced inflammation in mice, on Slc25a39/40 expression. Additionally, we used human clear cell renal carcinoma (KMRC-1) cells to elucidate the mechanism of regulation of SLC25A39/40 expression in the kidneys after LPS treatment. BDL resulted in a decrease in Slc25a39 mRNA in the liver and a decrease in Slc25a39/40 mRNA and protein in the kidneys. Consequently, there was a significant decrease in mGSH levels in the kidneys of BDL mice compared with those in sham mice. LPS treatment resulted in increased Slc25a40 expression in the kidneys. In KMRC-1 cells, the combination treatment of LPS-RS or FPS-ZM1 with LPS suppressed the LPS-induced increase in SLC25A40, suggesting that SLC25A40 expression could be regulated by the signaling pathway via toll-like receptor 4 and the receptor for advanced glycation end products, respectively. Our findings contribute to understanding the role of mGSH in the maintenance of the mitochondrial redox state. To the best of our knowledge, this is the first study that demonstrates the changes in Slc25a39/40 expression in mice with cholestasis-associated renal injury and LPS-induced inflammation.

Bile Acids in Intrahepatic Cholestasis of Pregnancy

“…The NLR family pyrin domain containing 3 (NLRP3) inflammasome in hepatic stellate cells and Kupffer cells is activated by BAs, causing inflammation or fibrosis [ 16 ]. The level of intracellular γ-glutamyl-L-cysteinyl-glycine (GSH), which protects cells against oxidative stress, cell proliferation, and division, is significantly influenced by inflammation and oxidative stress related to cholestasis [ 17 ]. Activation of the NF-κB pathway through the G protein-coupled BA receptor 1 (GPBAR1) is induced by BAs, resulting in elevated levels of inflammatory genes in trophoblasts, abnormal leukocyte infiltration, and placental inflammation [ 12 ].…”