Corticosterone accelerates hypoxia- and cyanide-induced ATP loss in cultured hippocampal astrocytes.
Glucocorticoids potentiate injury to the rodent hippocampus following a variety of metabolic insults, including hypoxia/ischemia, both in vitro and in vivo. We have examined whether corticosterone (CORT), the principal glucocorticoid in the rat, could exacerbate hypoxic energy failure in cultured hippocampal astrocytes. Exposure to 6 h of atmospheric hypoxia (100% N2) or to 30 min of cyanide did not cause any detectable cell injury, although moderate astrocyte damage did occur alter 6 h of hypoxia in the absence of glucose. Both cyanide and hypoxia significantly reduced astrocyte ATP content, a decline that was further reduced when glucose was omitted. A 30 min exposure to 100 microM glutamate elevated ATP content under normoxic conditions but enhanced the cyanide-induced loss of ATP. A 24 h pre-treatment with CORT did not influence normoxic ATP levels but potentiated the loss of ATP following both cyanide and hypoxia. CORT also exacerbated the loss of ATP seen after combined exposure to cyanide and glutamate, as well as that following cyanide + 0 mM glucose. These results indicate that both CORT and glutamate can potentiate hypoxia-induced energy failure in hippocampal astrocytes, albeit by different mechanisms.
Tombaugh
G C
GC
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710.
Sapolsky
R M
RM
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D003345:Corticosterone / Q000494:pharmacology*; D003486:Cyanides / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats
D003486:Cyanides; D005971:Glutamates; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D003345:Corticosterone