[Stress response of cultured astrocytes to hypoxia/reoxygenation]

As the most abundant cell type in the central nervous system (CNS), astrocytes play a major role in the host defense mechanism even in situations associated with ischemic cerebrovascular diseases. Cultured rat astrocytes exposed to hypoxia (pO2 = 8-10 torr) expressed a set of stress proteins whose Mrs are 28, 33, 78, 94, and 150 kDa. Northern/western blot analysis indicated that these stress proteins are identical to heme oxygenase-1 (33 kDa), 78-kDa glucose regulated protein (GRP78) and GRP94 (94 kDa), respectively. The amino acid sequence analysis of the 150-kDa protein revealed that it (ORP150: oxygen regulated protein) is a novel stress protein belonging to the heat shock protein family. The induction of this stress protein was seen in the endoplasmic reticulum (ER) and mainly regulated by the decline of atmospheric oxygen tension, not by other chemical stimuli. The abundant expression of these ER-localized stress proteins (ORP150, GRP94 and GRP78) suggest that the stress response of these astrocytes to hypoxia may focus on the restoration of ER function. The unique expression of these stress proteins may provide a clue to understand the role of this cell type in ischemic cerebrovascular accidents.