Platelets from patients with type 2 diabetes demonstrate hyper-aggregability and contribute to the vascular complications of the disease. We have found that type 2 diabetes and peroxynitrite (ONOO-) can elicit the tyrosine nitration and inactivation of the endoplasmic reticulum Ca2+- ATPase (SERCA-2), which results in elevated platelet [Ca2+]i and the activation of μ-calpain. The latter is responsible for the limited proteolysis of a series of platelet proteins. The aim of this proposal is to determine the consequences of the redox changes associated with type 2 diabetes on platelet function; concentrating initially on the alterations in platelet signaling induced by μ- calpain and the vascular consequences of the μ-calpain-modified platelet-derived products.

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