Involvement of Na+/H+ exchanger 1 in advanced glycation end products-induced proliferation of vascular smooth muscle cell.
In this present study, we examined the role of Na(+)/H(+) exchanger 1 (NHE1) in the cultured rat vascular smooth muscle cell (VSMC) proliferation induced by advanced glycation end products (AGEs). AGEs significantly increased the [(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(i)) was significantly increased after 24h exposure to AGEs (10mug/ml). The direct AGEs-induced NHE1 activation was measured by the Na(+)-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 24h. These findings demonstrate NHE1 is required for in AGEs-induced proliferation of VSMC, and AGEs increase NHE1 activity via the MAPK pathway.
Wu
Shujin
S
Department of Pharmacology, Pharmaceutical College, Central South University, No. 110 Xiang-Ya Road, Changsha, Hunan 410078, China.
Song
Tao
T
Zhou
Shouhong
S
Liu
Yuhui
Y
Chen
Gengrong
G
Huang
Ningjiang
N
Liu
Liying
L
D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000378:metabolism; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology
D017127:Glycation End Products, Advanced; D006146:Guanidines; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C452850:Slc9a1 protein, rat; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide; D020929:Mitogen-Activated Protein Kinase Kinases