Title

Biology of Hypoxia

Authors

Juliann G. Kiang;K.T. Tsen

Key Words

hypoxia ; iNOS ; caspase ; ATP ; calcium ; NO ; free radical

PublicationName

The Chinese Journal of Physiology

Volume or Term/Year and Month of Publication

49卷5期(2006 / 10 / 31)

Page #

223 - 233

Content Language

英文

English Abstract

Hypoxia is an often seen problem resulting from conditions such as ischemia, hemorrhage, stroke, premature birth, and other cardiovascular difficulties. To find useful remedies that are capable of ameliorating its casualty is an essential effort. Although the underlying mechanisms of the hypoxia induce injury and cell death are still not fully understood, it has been shown that hypoxia induces nitric oxide (NO) overproduction and inducible nitric oxide synthase (iNOS) overexpression that play important roles in producing injury including increases in polymorphonuclear neutrophils (PMN) infiltration to injured tissues and leukotriene B4 (LTB4) generation. Moreover, it has been evident that transcription factors responsible for iNOS expression are also altered by hypoxia. Hypoxia also increases intracellular Ca(superscript 2+) concentration, tumor necrosis factor-α, lipid peroxidation, prostaglandin E2 production, activity of caspase-3 and -9, and release of cytochrome c from mitochondria, apoptosis inducible factor, and endonuclease G. However, it has been shown that downregulation of iNOS can limit cell injury caused by hypoxia. In our laboratory, we have found that treatment with either iNOS inhibitors or iNOS siRNA inhibits iNOS expression, reduces lipid peroxidation, apoptosome formation, and cellular caspase-3 activity, preserves cellular ATP levels, and increases cell survival. Therefore, iNOS inhibition may be a novel mechanism for protection from hypoxia-induced injury and cell death.

Topic Category 醫藥衛生 > 基礎醫學
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