期刊
BIOFACTORS
卷 45, 期 4, 页码 607-615出版社
WILEY
DOI: 10.1002/biof.1517
关键词
high glucose; sRAGE; THP-1; TRPC; 18 beta-glycyrrhetinic acid
资金
- Ministry of Science and Technology, Taiwan [107-2320-B-005-009]
Enhancing soluble receptor for advanced glycation endproducts (sRAGE) is considered as a potent strategy for diabetes therapy. sRAGE secretion is regulated by calcium and transient receptor potential canonical (TRPC) channels. However, the role of TRPC channels in diabetes remains unknown. 18 beta-Glycyrrhetinic acid (18 beta-GA), produced from liquorice, has shown antidiabetic properties. This study was aimed to investigate the effect of 18 beta-GA on sRAGE secretion via TRPC channels in high glucose (HG)-induced THP-1 cells. HG treatment enhanced TRPC3 and TRPC6 expression and consequently caused reactive oxygen species (ROS) accumulation mediated through p47 nicotinamide-adenine dinucleotide phosphate oxidase and inducible nitric oxide synthase (iNOS) associated with uncoupling protein 2 (UCP2) decline and lower sRAGE secretion. Interestingly, 18 beta-GA showed the dramatic effects similar to Pyr3 or 2-aminoethyl diphenyl borinate inhibitors and effectively reversed HG-elicited mechanisms including that blocking TRPC3 and TRPC6 protein expressions, suppressing intracellular [Ca2+] concentration, decreasing expressions of ROS, p47s, and iNOS, but increasing UCP2 level and promoting sRAGE secretion. Therefore, 18 beta-GA provides a potential implication to diabetes mellitus and its complications.
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