Abalenikhina Yulia V, Shchulkin Aleksey V, Suchkova Olga N, Ananyeva Pelageya D, Mylnikov Pavel Yu, Yakusheva Elena N, Suchkov Igor A, Kalinin Roman E
Department of Biological Chemistry, Ryazan State Medical University, 390026 Ryazan, Russia.
Department of Pharmacology, Ryazan State Medical University, 390026 Ryazan, Russia.
Biomolecules. 2025 Mar 17;15(3):428. doi: 10.3390/biom15030428.
S-nitrosoglutathione (GSNO) is the S-nitrosated derivative of glutathione (GSH). GSNO is an endogenous class of NO donors and a natural NO depot in biological systems. Organic anion transporting polypeptide 1B1 (OATP1B1) is an influx transporter that is expressed in the liver. OATP1B1 plays an important role in the transport of endogenous and exogenous substances. Various pathways for the regulation of OATP1B1 have been described. In the present study, the involvement of OATP1B1 in GSNO transport and the regulation of OATP1B1 by GSNO was examined. For HEK293-OATP1B1, it has been shown that GSNO is not a substrate of OATP1B1, but OATP1B1 can participate in the transport of GSH across the cell membrane. GSNO at concentrations of 1-100 μM and exposure for 3 h do not affect the expression and activity of OATP1B1, but exposure for 24 and 72 h stimulates the expression of the gene, OATP1B1, and transporter activity. Up-regulation of OATP1B1 by GSNO is carried out through the NO-cGMP signaling pathway, Nrf2, and LXR.
S-亚硝基谷胱甘肽(GSNO)是谷胱甘肽(GSH)的S-亚硝化衍生物。GSNO是一类内源性一氧化氮供体,也是生物系统中的天然一氧化氮储存库。有机阴离子转运多肽1B1(OATP1B1)是一种在肝脏中表达的摄取转运体。OATP1B1在内外源性物质的转运中起重要作用。已有多种调节OATP1B1的途径被描述。在本研究中,检测了OATP1B1在GSNO转运中的作用以及GSNO对OATP1B1的调节。对于HEK293-OATP1B1,已表明GSNO不是OATP1B1的底物,但OATP1B1可参与谷胱甘肽跨细胞膜的转运。浓度为1-100μM的GSNO作用3小时不影响OATP1B1的表达和活性,但作用24小时和72小时可刺激OATP1B1基因的表达及转运体活性。GSNO对OATP1B1的上调是通过NO-cGMP信号通路、Nrf2和LXR实现的。