Endothelin-1 protects astrocytes from hypoxic/ischemic injury.
Under pathological conditions such as ischemia (I), subarachnoid hemorrhage, and Alzheimer's disease, astrocytes show a large increase in endothelin (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 conditions, astrocytes from wild-type and ET-1-deficient mice showed no difference in their morphology and cell proliferation rates. ET-3 and ETA receptor mRNAs were up-regulated whereas ETB 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 feedback 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 vulnerable to H and H/I injuries and that the up-regulation of astrocytic ET-1 is essential for the survival of astrocytes.
Institute of Molecular Biology, The University of Hong Kong, Pokfulam.
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MC
Ho
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Lo
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H
Kurihara
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Yu
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Chung
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Chung
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D001923:Brain Chemistry; D002455:Cell Division; D015687:Cell Hypoxia; D048429:Cell Size; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D019334:Endothelin-3 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018696:Neuroprotective Agents; D012333:RNA, Messenger / Q000378:metabolism; D017466:Receptors, Endothelin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016895:Culture Media, Serum-Free; D019332:Endothelin-1; D019334:Endothelin-3; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D017466:Receptors, Endothelin; D007770:L-Lactate Dehydrogenase