Department of Biochemistry, Pharmacy Faculty for Girls, Al-Azhar University, Cairo, Egypt.
Department of Biochemistry, National Organization for Drug Control and Research (NODCAR), Giza, Egypt.
J Biochem Mol Toxicol. 2018 Jan;32(1). doi: 10.1002/jbt.22014. Epub 2017 Dec 29.
Proximal tubule protein take-up is interceded by 2 receptors, megalin and cubilin. These receptors rescue an assortment of filtered ligands including fundamental vitamins and hormones. The objective of this study was to investigate the potential relation of megalin receptor injury with nuclear factor-kappa B (NF-κB) upregulation in acute kidney injury rat model. Twenty four rats were allocated into two groups: control group received saline, while the second group was intoxicated with cadmium chloride (2.4 mg Cd/kg/day i.p) for 30 days. Blood urea nitrogen, serum creatinine, tissue oxidant-antioxidant parameters (malondialdehyde [MDA] and reduced glutathione [GSH]) and expression levels for NF-κB, toll like receptor-2 (TLR2), toll like receptor-4 (TLR4), and megalin receptor were estimated. Noticeable downregulation of megalin receptor versus upregulation of NF-κB, TLR2, and TLR4 were observed in AKI rat model together with significant elevation in MDA as well as significant reduction in GSH. The study concluded that the oxidative stress in kidney tissue leads to megalin receptor damage, which indeed motivates upregulation of NF-κB through TLRs 2 and 4 pathways.
近端肾小管蛋白摄取由 2 种受体（巨球蛋白和 Cubilin）介导。这些受体可回收多种滤过性配体，包括基本维生素和激素。本研究旨在探讨急性肾损伤大鼠模型中巨球蛋白受体损伤与核因子-κB（NF-κB）上调之间的潜在关系。24 只大鼠随机分为两组：对照组给予生理盐水，第二组用氯化镉（2.4mgCd/kg/天腹腔注射）处理 30 天。测定血尿素氮、血清肌酐、组织氧化应激参数（丙二醛[MDA]和还原型谷胱甘肽[GSH]）以及 NF-κB、Toll 样受体-2（TLR2）、Toll 样受体-4（TLR4）和巨球蛋白受体的表达水平。在 AKI 大鼠模型中，巨球蛋白受体明显下调，NF-κB、TLR2 和 TLR4 明显上调，MDA 显著升高，GSH 显著降低。研究结论认为，肾组织中的氧化应激导致巨球蛋白受体损伤，通过 TLRs2 和 4 途径确实促使 NF-κB 上调。
