Effects of advanced glycosylation end products on interactions between cis-elements and trans-acting factors of hepatic insulin receptor gene
10.3760/cma.j.issn.1000-6699.2009.01.005
- VernacularTitle:晚期糖基化终末产物对胰岛素受体顺式调控元件和反式作用因子相互作用的影响
- Author:
Jian RONG
;
Changqing YU
;
Pei YANG
- Publication Type:Journal Article
- Keywords:
Diabetes mellitus;
Aging;
Glycosylation end products,advanced;
Human insulin receptor promoter;
Hepatic nuclear factor
- From:
Chinese Journal of Endocrinology and Metabolism
2009;25(1):17-21
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects of advanced glyeosylation end products (AGEs) on the binding of hepatic nuclear factors to the human insulin receptor (hlR) gene promoter. Methods The oligonueleotides with hlR gene promoter activity, 42 bp (spanning -1 441 to -1 400, US1) or 146 bp (spanning -638 to -493), were artificially synthesized, with point mutations at 5 key G residues in 42 bp US1 m5 oligonucleotides. US1 and rat hepatic nuclear extracts (HNE) were incubated with glucose 6-phosphate, prior to non-competition and competition gel retardation electrophoresis. Results Competition gel retardation electrophoresis showed that the binding capacity of 32p-labeled US1 probe to HNE could be signifficantly decreased with increased US1. US1-AGEs and US1m5 decreased the binding of probe to HNE as well, but only partly affected the electrophoretie bands [1,5,10 ng US1-AGEs: (41.08±2.86)%, (27.64±2.92)%, (15.35±1.81%) vs (52.05±1.79)%]; 5,10 ng US1m5: (5.20± 1.03)%, (1.81±0.21)% vs (52.05±1.79)%]. AGEs formed on HNE could increase the binding of HNE to probe, along with nonspecifie binding increasing. Conclusion The impact of AGEs on hlR gene expression seems to be related to the effects on cis-elements and trans-acting factors.
