Endothelin‐1 protects astrocytes from hypoxic/ischemic injury

ABSTRACT Under pathological conditions such as ischemia (I), subarachnoid hemorrhage, and Alzhei¬mer's disease, astrocytes show a large increase in endo¬thelin (ET) ‐like immunoreactivity. However, it is not clear whether ET is protective or destructive to these cells during brain injury. Using astrocytes from ET‐1‐deficient mice, we determined the effect of ET‐1 on these cells under normal, hypoxic (H), and hypoxic/ ischemic (H/I) conditions. Under normal culture con¬ditions, astrocytes from wild‐type and ET‐1‐deficient mice showed no difference in their morphology and cell proliferation rates. ET‐3 and ET A receptor mRNAs were up‐regulated whereas ET B receptor mRNA was down‐regulated in ET‐1‐deficient astrocytes, suggesting that ET‐1 and ET‐3 may complement each other's functions and that the expressions of these endothelins and their receptors are regulated by a complex feed¬back mechanism. Under H and H/I conditions, ET‐1 peptide and mRNA were up‐regulated in wild‐type astrocytes, and the astrocytes without ET‐1 died faster than the wild‐type astrocytes, as indicated by greater efflux of lactate dehydrogenase. The present study suggests that astrocytes without ET‐1 are more vulner¬able to H and H/I injuries and that the up‐regulation of astrocytic ET‐1 is essential for the survival of astrocytes.—Ho, M. C. Y., Lo, A. C. Y., Kurihara, H., Yu, A. C. H., Chung, S. S. M., Chung, S. K. Endothelin‐1 protects astrocytes from hypoxic/ischemic injury. FASEB J. 15, 618‐626 (2001)