Involvement of Na{sup +}/H{sup +} exchanger 1 in advanced glycation end products-induced proliferation of vascular smooth muscle cell
- Department of Pharmacology, Pharmaceutical College, Central South University, No. 110 Xiang-Ya Road, Changsha, Hunan 410078 (China)
In this present study, we examined the role of Na{sup +}/H{sup +} exchanger 1 (NHE1) in the cultured rat vascular smooth muscle cell (VSMC) proliferation induced by advanced glycation end products (AGEs). AGEs significantly increased the [{sup 3}H] thymidine incorporation of VSMC. Cariporide, an NHE1 inhibitor, dose-dependently attenuated the AGEs-induced increase in cell DNA synthesis. Thus the effect of AGEs on NHE1 activity was next examined. The cariporide-dependent intracellular pH (pH{sub i}) was significantly increased after 24 h exposure to AGEs (10 {mu}g/ml). The direct AGEs-induced NHE1 activation was measured by the Na{sup +}-dependent intracellular pH recovery from intracellular acidosis. AGEs can increase the NHE1 activity in a time- and concentration-dependent manner. Inhibition of either the receptor for AGEs (RAGE) by anti-RAGE or mitogen-activated protein kinases (MAPK) by PD98059 reversed the effect of AGEs on NHE1 activity. Reverse transcription (RT)-PCR analysis revealed that AGEs dose-dependently increased NHE1 mRNA at 24 h. These findings demonstrate NHE1 is required for in AGEs-induced proliferation of VSMC, and AGEs increase NHE1 activity via the MAPK pathway.
- OSTI ID:
- 21143909
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 375; ISSN BBRCA9; ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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