Role of Annexin II in Peripheral Vascular Disease

Background
Chronic exposure to arsenic frequently results in peripheral vasular disease, as well as skin, lung, bladder, and kidney cancer. Recent evidence demonstrates that arsenite inhibits the production of plasmin which is necessary to dissolve blood clots in the vasulature. Our published studies with arsenic have demonstrated that the serine/threonin kinase, MEKK4, is involved in arsenic signal transduction, along with the calcium binding protein, annexin II.

Figure shows two proposed mechanisms for regulation of plasmin.

Goal
To understand the molecular mechanism by which arsenic causes its deleterious effects on the vascular system and how the activity of annexin II contributes to arsenic toxicity.

2. To characterize the interaction between annexin II and MEKK4.

3. To characterize arsenic-dependent regulation of PAI-1 and PAI-2.

4.To assess specific functions of annexin II.

Contact
Richard R. Vaillancourt
vaillancourt@pharmacy.arizona.edu
(520) 626-4374