Inhibition of Advanced Glycation End Products AGEs Accumulation by Pyridoxamine Modulates Glomerular and Mesangial Cell Estrogen Receptor α Expression in Aged Female MiceReport as inadecuate




Inhibition of Advanced Glycation End Products AGEs Accumulation by Pyridoxamine Modulates Glomerular and Mesangial Cell Estrogen Receptor α Expression in Aged Female Mice - Download this document for free, or read online. Document in PDF available to download.

Age-related increases in oxidant stress OS play a role in regulation of estrogen receptor ER expression in the kidneys. In this study, we establish that in vivo 17β-estradiol E2 replacement can no longer upregulate glomerular ER expression by 21 months of age in female mice anestrous. We hypothesized that advanced glycation end product AGE accumulation, an important source of oxidant stress, contributes to these glomerular ER expression alterations. We treated 19-month old ovariectomized female mice with pyridoxamine Pyr, a potent AGE inhibitor, in the presence or absence of E2 replacement. Glomerular ERα mRNA expression was upregulated in mice treated with both Pyr and E2 replacement and TGFβ mRNA expression decreased compared to controls. Histological sections of kidneys demonstrated decreased type IV collagen deposition in mice receiving Pyr and E2 compared to placebo control mice. In addition, anti-AGE defenses Sirtuin1 SIRT1 and advanced glycation receptor 1 AGER1 were also upregulated in glomeruli following treatment with Pyr and E2. Mesangial cells isolated from all groups of mice demonstrated similar ERα, SIRT1, and AGER1 expression changes to those of whole glomeruli. To demonstrate that AGE accumulation contributes to the observed age-related changes in the glomeruli of aged female mice, we treated mesangial cells from young female mice with AGE-BSA and found similar downregulation of ERα, SIRT1, and AGER1 expression. These results suggest that inhibition of intracellular AGE accumulation with pyridoxamine may protect glomeruli against age-related oxidant stress by preventing an increase of TGFβ production and by regulation of the estrogen receptor.



Author: Simone Pereira-Simon , Gustavo A. Rubio , Xiaomei Xia, Weijing Cai, Rhea Choi, Gary E. Striker, Sharon J. Elliot

Source: http://plos.srce.hr/



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