Vovk O. Role of NO-dependent signalling in the regulation of morphology and functional state of platelets under type 1 diabetes mellitus

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0405U002389

Applicant for

Specialization

  • 03.00.11 - Цитологія, гістологія

10-06-2005

Specialized Academic Board

К 35.246.01

Essay

The object : platelets of rats and humans under normal and diabetic state. The aim : approaches to correction of metabolic disorders leading to occurence and development of diabetic complications. Methods of studies: determination of enzyme activities, aggregation analysis, Western- blotting, electrophoresis in polyacrylamide gel, electronic microscopy, in vitro GST-binding assay. It was found that changes in structure and functional state of platelets under type 1 diabetes mellitus (DM) are caused by changes in proportion between activities of constitutive and inducible isoforms of nitric oxide synthase (iNOS). Using western immunoblots of intraplatelet proteins of healthy persons and patients suffered from type 1 DM, increased expression of iNOS and p85 alfa regulatory subunit of phosphatidylinositol-3-kinase (PI-3-kinase) was observed in diabetic platelets. Translocation dynamics of PI-3-kinase regulatory subunit into cytoskeletal fraction during ADP-induced platelet aggregation and after wortmannintreatment was studied. We propose that aminoguanidine may be used to search for new drugs for treatment and prevention of vascular complications under type 1 diabetes mellitus. Field of application: cell biology and medicine

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