Nemecz M.,Institute Of Cellular Biology And Pathology Nsimionescu |
Popov D.,Institute Of Cellular Biology And Pathology Nsimionescu |
Georgescu A.,Institute Of Cellular Biology And Pathology Nsimionescu
Annals of the Romanian Society for Cell Biology | Year: 2010
Protein activation by phosphorylation reactions (exerted by various kinases) is a universal mechanism of signal transduction that controls the amplitude of signaling response. In physiological conditions, this mechanism is fine tuned by dephosphorylation reactions (exerted by phosphatases), that control the rate and the duration of signaling response. In this study we questioned on the in vivo effect of circulating high glucose concentration on the balance between phosphorylating kinases and dephosphorylating protein tyrosine phosphatase 1B operating in the aorta, an issue still uncovered. Experiments were conducted on Type 1 diabetic golden Syrian hamsters, at 4 weeks after streptozotocin injection (control: normal hamsters); animals were severely diabetic (plasma glucose concentration: 440±20 mg/dl), the pancreatic β cells showed progressive destruction and apoptosis, and the thoracic aorta displayed dysfunctional endothelium and smooth muscle cells. In comparison with normal animals, hyperglycaemia produced the following effects on aortic signaling proteins expression: (i) did not significantly alter the protein level of insulin receptor substrate 2 (IRS2, that mediates effects of insulin, insulin-like growth factor 1, and other cytokines by acting as a molecular adaptor between diverse receptor tyrosine kinases and downstream effectors), (ii) up-regulates expression of Protein Tyrosine Phosphatase-1B (PTP-1B, that interacts with and dephosphorylates the activated insulin receptor), and (iii) down-regulates the levels of Phosphoinositide 3-kinase (PI3K, that interacts with the insulin receptor substrate and regulates intracellular glucose uptake through a series of phosphorylation events), and AKT (a member of the serine/threonine-specific protein kinase family). The imbalance in hyperglycaemia - induced phosphorylation /dephosphorylation events are likely to intervene in diabetes-associated aortic wall dysfunction.