Up-regulation of heme oxygenase-1 by isoflurane preconditioning during tolerance against neuronal injury induced by oxygen glucose deprivation.
Heme oxygenase (HO) is the rate-limiting enzyme in the degradation of heme to produce bile pigments and carbon monoxide. The HO-1 isozyme is induced by a variety of factors such as heat, heme, ischemia, and hydrogen peroxide. In recent years, mounting findings have suggested that HO-1 has a neuroprotective activity against ischemic injury. The neuroprotective role of isoflurane, a commonly used anesthetic, has been well documented, but little is known about the underlying mechanisms involved. Recently, isoflurane has been shown to up-regulate HO-1 in the liver. In this study, we show that isoflurane preconditioning promotes the survival of cultured ischemic hippocampal neurons by increasing the number of surviving neurons and their viability. Further study by reverse transcription-polymerase chain reaction and Western blot analysis showed that isoflurane preconditioning significantly increases HO-1 expression in oxygen glucose deprivation (OGD)-induced neuronal injury. Furthermore, inhibition of HO activity by tin protoporphyrin partially abolishes isoflurane preconditioning's protective effect as measured by lactate dehydrogenase release in OGD neurons. These findings indicated that the neuroprotective role of isoflurane preconditioning against OGD-induced injury might be associated with its role in up-regulating HO-1 in ischemic neurons.
Li
Qifang
Q
Department of Anesthesiology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Zhu
Yesen
Y
Jiang
Hong
H
Xu
Hui
H
Liu
Heping
H
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004361:Drug Tolerance / Q000235:genetics / Q000502:physiology; D005947:Glucose / Q000172:deficiency; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D019194:Ischemic Preconditioning / Q000379:methods*; D007530:Isoflurane / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects*
D018685:Anesthetics, Inhalation; D007530:Isoflurane; D051547:Heme Oxygenase-1; D005947:Glucose