Amadori-glycated albumin-induced vascular smooth muscle cell proliferation and expression of inhibitor of apoptosis protein-1 and nerve growth factor-gamma.
We investigated the effects of Amadori-glycated serum albumin (GSA) on cell proliferation as well as expressions of antioxidant enzyme genes and marker genes associated with signal transduction pathways in rat aortic vascular smooth muscle cells (VSMCs). Quiescent VSMCs treated with GSA (0-500 microg/mL, 48 h) exhibited a dose-dependent increase in proliferation that was prevented by PD98059 (25 microM), suggesting a MAPK-dependent signaling pathway. Compared with bovine serum albumin (BSA)-treated cells, the GSA (500 microg/mL, 24~h)-treated VSMCs showed a higher superoxide dismutase 2 gene expression in quantitative RT-PCR, suggesting the involvement of oxidative stress. In a focused oligonucleotide array containing 96 signal transduction-related genes, expression of inhibitor of apoptosis protein-1 (IAP-1), nerve growth factor-gamma (NGF-gamma), and c-jun genes was significantly higher in the GSA-treated VSMCs. These results suggest that induction of antiapoptotic proteins like IAP-1 and strong mitogens like NGF-gamma by GSA might further contribute to the VSMC proliferation and accelerated vascular remodeling in diabetes.
Lee
Byung-Wan
BW
Department of Internal Medicine, Hallym University, Chuncheon, Korea.
Ihm
Jahei
J
Kang
Jun Gu
JG
Choi
Moon Gi
MG
Yoo
Hyung Joon
HJ
Ihm
Sung-Hee
SH
D000818:Animals; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D017127:Glycation End Products, Advanced; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics*; D012709:Serum Albumin / Q000494:pharmacology*; D000093423:Glycated Serum Albumin
D017127:Glycation End Products, Advanced; D051034:Inhibitor of Apoptosis Proteins; D009414:Nerve Growth Factors; D012709:Serum Albumin; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; C494836:Birc3 protein, rat; D012697:Serine Endopeptidases; C079910:nerve growth factor, gamma; D000093423:Glycated Serum Albumin