Hypoxia-inducible factor-1 alpha has a key role in hypoxic preconditioning.
Sublethal hypoxia induces tolerance to subsequent hypoxic insults in a process known as hypoxic preconditioning (HP). Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a key transcription protein involved in the mechanism of HP. In this study, we investigated the effects of HP on tissue oxygenation and expression of HIF-1 alpha gene targets in the brain using neural cell-specific HIF-1 alpha-deficient mice. The animals were exposed to 8% oxygen for 3 hours. Twenty-four hours later, the oxygen partial pressure (pO(2)) of brain tissue and gene expression were measured during hypoxia. HP improved the pO(2) of brain tissue during subsequent hypoxia with upregulated inducible nitric oxide synthase in wild-type mice, whereas HP had no detectable effect in the mutant mice. Our results indicate that the protective effects of HP may be partially mediated by improving tissue oxygenation via HIF-1 alpha and inducible nitric oxide synthase.
Taie
Satoshi
S
Department of Anesthesiology and Emergency Medicine, Kagawa University, Ikenobe, Miki-cho, Kagawa, Japan. taie@med.kagawa-u.ac.jp
Ono
Junichiro
J
Iwanaga
Yasuyuki
Y
Tomita
Shuhei
S
Asaga
Takehiko
T
Chujo
Kosuke
K
Ueki
Masaaki
M
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000201:enzymology / Q000378:metabolism*; D015870:Gene Expression; D000860:Hypoxia / Q000201:enzymology / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D019194:Ischemic Preconditioning; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D016133:Polymerase Chain Reaction
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D052247:Nitric Oxide Synthase Type II; D010100:Oxygen