THE 70 KILODALTON HEAT SHOCK PROTEIN (HSP70) IS A HIGHLY CONSERVED CYTOPLASMIC CONSTITUENT WHOSE SYNTHESIS IS STIMULATED BY MANY DIFFERENT TYPES OF METABOLIC STRESS. ACCUMULATION OF HSP70 IN THE CELL CORRELATES WITH IMPROVED CELL SURVIVAL FOLLOWING ACUTE METABOLIC STRESS AND IT IS HYPOTHESIZED THAT ELEVATED HSP70 PRESERVES THE FUNCTION OF OTHER VITAL CYTOPLASMIC COMPONENTS DURING A PERIOD OF ABNORMAL CONDITIONS. WE HAVE PRELIMINARY EVIDENCE IN SEVERAL MODEL SYSTEMS THAT HSP70 ADDED TO THE EXTRACELLULAR FLUID ALSO CAN PROTECT CELLS FROM DAMAGE. FACILITIES AT THE NVPF HAVE BEEN USED TO EXAMINE THE MECHANISMS BY WHICH EXTERNAL HSP 70 APPLICATION PROTECTS CELLS FROM DAMAGE. TWO PROCEDURES HAVE BEEN USED BOTH INVOLVING PROBE TECHNOLOGY (CA2+ FLUX DETECTION) AND MICROSCOPY. A) PRELIMINARY STUDIES INDICATE THAT HSP 70 CAN PROTECT CELLS FROM FREE RADICAL DAMAGE. B) EXOGENOUSLY APPLIED HSP 70 HAS BEEN OBSERVED TO MODULATE THE STEADY-STATE TRANSMEMBRANE CALCIUM EFFLUX. THIS LATTER OBSERVATION IS OUR MOST RECENT AND HAS NOW BEEN COUPLED TO CONFOCAL IMAGING OF FREE-CYTOSOLIC CALCIUM LEVELS DURING HSP 70 APPLICATION. HSP 70 BOTH INCREASES THE TRANSMEMBRANE EFFLUX AND REDUCES THE FREE CALCIUM LEVELS. WE HYPOTHESISE THAT THESE EVENTS RESULT IN A CELLULAR PROTECTION FROM CALCIUM INDUCED DAMAGE. OVER THE COMING MONTHS THIS STUDY WILL BE EXPANDED TO EXAMINE OTHER HSP AS WELL AS `-CRYSTALLIN. THE LATTER WILL BE DONE IN COLLABORATION WITH DR. A. SPECTOR OF COLUMBIA UNIVERSITY COLLEGE OF PHYSICIANS AND SURGEONS. DR. SPECTOR RECEIVED AN NIH MERIT AWARD IN 1988.
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