Long-term high glucose concentration influences Akt, ERK1/2, and PTP1B protein expression in human aortic smooth muscle cells.
Hyperglycemia stimulates a plethora of intracellular signaling pathways within the cells of the vascular wall resulting in dysfunction-associated pathologies. Most of the studies reported so far explored the effect of rather short-time exposure of smooth muscle cells to high glucose concentrations. To mimic situation in Type 2 diabetes in which vascular wall is constantly exposed to circulating hyperglycemia, we report here the long-term (7days) effect of high glucose concentration on human media artery smooth muscle cells. This consists in up-regulation of PTP1B protein expression, down-regulation of basal Akt phosphorylation, and elevation of basal ERK1/2 activation. Acute stimulation of cells in high glucose with insulin down-regulated PTP1B expression, slightly decreased ERK1/2 activity, and activated Akt, whereas oxidative stress up-regulated Akt and ERK1/2 phosphorylation. In conclusion, long-term high glucose and acute oxidative stress and insulin stimulation imbalance the expression of activated kinases Akt and ERK1/2 and of dephosphorylating PTP1B in the insulin signaling pathway.
Popov
Doina
D
Institute of Cellular Biology and Pathology "N. Simionescu", Bucharest, Romania. doina.popov@icbp.ro
Nemecz
Miruna
M
Dumitrescu
Madalina
M
Georgescu
Adriana
A
Böhmer
Frank D
FD
D001011:Aorta / Q000187:drug effects / Q000201:enzymology*; D002478:Cells, Cultured; D015536:Down-Regulation; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D006943:Hyperglycemia / Q000201:enzymology; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis*; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology*; D018384:Oxidative Stress; D010766:Phosphorylation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000096:biosynthesis*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis*; D015854:Up-Regulation
D007328:Insulin; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D005947:Glucose