OTKA F038149

Principal Investigator: Peter Csutora M.D., Ph.D.

Institution: Department of Clinical Chemistry

University of Pécs, Faculty of Medicine

Ifjúság u. 13, Pécs, 7624, Hungary

e-mail: peter.csutora@aok.pte.hu

OTKA supported period: 2002 - 2005

Title: Calcium influx factor – metabolism and role in the development of T-cell deficiencies seen in diabetes mellitus.

Calcium influx factor is the postulated signalling molecule that transmits the signal of endoplasmic reticulum calcium depletion to the plasma membrane calcium channels and thus activates capacitative calcium entry. This molecule plays a crucial role in the regulation of intracellular calcium levels. It has been hypothesized that its decreased or altered production is responsible for a wide variety of cellular disorders. In the present proposal we seek to investigate:

1. What are the precursors of CIF, and what are the major steps and enzymes in its synthetic pathway? How does it activate plasma membrane calcium channels?

2. One of the most important immunological complications in diabetes mellitus is the decreased cytokine production of T-lymphocytes. Our preliminary data suggests that this is at least in part due to decreased CIF synthesis or the lack of response to normal CIF levels within diabetic individuals. This results in decreased or missing capacitative calcium entry through the plasma membrane calcium channels. We seek to further investigate the underlying mechanisms, and also to find pharmacological agents that would restore the cytokine production of lymphocytes to normal levels.