EXPOSURE OF ASTROCYTES TO HYPOXIA REOXYGENATION ENHANCES EXPRESSION OF GLUCOSE-REGULATED PROTEIN-78 FACILITATING ASTROCYTE RELEASE OF THE NEUROPROTECTIVE CYTOKINE INTERLEUKIN-6

Astrocytes exposed to hypoxia(H) or hypoxia/reoxygenation (H/R) mainta in cell viability and display changes in protein biosynthesis, Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of metabolically la beled astrocytes exposed to H showed induction of an approximate to 78 -kDa polypeptide that demonstrated sequence identity with glucose-regu lated protein (GRP) 78. Cell lysates from H/R astrocytes displayed ind uction of neuroprotective interleukin (IL) 6, which was present in a h igh-molecular-weight complex also containing GRP78, suggesting that GR P78 might be functioning as a chaperone during cellular stress consequ ent on H/R. Introduction of antisense oligonucleotide to GRP78 into as trocytes prevented expression of the protein and suppressed H/R-induce d astrocyte release of IL-6 by approximate to 50%. These data indicate that modulation of astrocyte properties during oxygen deprivation res ults, in part, from intracellular glucose depletion and subsequent exp ression of GRP78, which sustains generation of neuroprotective IL-6 un der the stress of H/R.