TY - JOUR
T1 - Biology of hypoxia
AU - Kiang, Juliann G.
AU - Tsen, Kong-Thon
N1 - Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2006
Y1 - 2006
N2 - 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 B 4 (LTB 4 ) generation. Moreover, it has been evident that transcription factors responsible for iNOS expression are also altered by hypoxia. Hypoxia also increases intracellular Ca 2+ concentration, tumor necrosis factor-α, lipid peroxidation, prostaglandin E 2 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.
AB - 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 B 4 (LTB 4 ) generation. Moreover, it has been evident that transcription factors responsible for iNOS expression are also altered by hypoxia. Hypoxia also increases intracellular Ca 2+ concentration, tumor necrosis factor-α, lipid peroxidation, prostaglandin E 2 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.
KW - ATP
KW - Calcium
KW - Caspase
KW - Free radical
KW - Hypoxia
KW - NO
KW - iNOS
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M3 - Review article
C2 - 17294830
AN - SCOPUS:33847758449
SN - 0304-4920
VL - 49
SP - 223
EP - 233
JO - Chinese Journal of Physiology
JF - Chinese Journal of Physiology
IS - 5
ER -