Activation of heme oxygenase-1 expression by disturbance of endoplasmic reticulum calcium homeostasis in rat neuronal cell culture.
Evidence has been presented that disturbances of endoplasmic reticulum (ER) calcium homeostasis contribute to neuronal injury induced by transient cerebral ischemia. The present series of experiments was designed to study whether the expression of heme oxygenase-1 (HO-1), which is markedly increased after transient cerebral ischemia, is also activated by a disturbance of ER calcium homeostasis. ER calcium pools were depleted by a 30 min exposure of primary cortical and hippocampal neurons to thapsigargin (Tg), an irreversible inhibitor of ER Ca2+-ATPase. In cortical neurons, HO-1 mRNA levels (analysed by quantitative polymerase chain reaction (PCR)) were significantly increased (22-fold) 12 h after exposure to Tg but had decreased again to only nine times control levels by 24 h after treatment. In hippocampal neurons, a significant increase in HO-1 mRNA levels was already apparent 4 h after treatment (8.3-fold over controls), levels rose further to 27-fold over controls after 6 h, and stayed high for up to 24 h after treatment (34-fold over controls). The similarity between the pattern of changes in HO-1 mRNA levels induced by transient ischemia and depletion of ER calcium stores suggests common underlying mechanisms.
Gissel
C
C
Max-Planck-Institute for Neurological Research, Department of Experimental Neurology, Cologne, Germany.
Doutheil
J
J
Paschen
W
W
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D006624:Hippocampus / Q000166:cytology; D006706:Homeostasis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019284:Thapsigargin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D019284:Thapsigargin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D002118:Calcium