Induced Adaptive Resistance to Oxidative Stress in the CNS: A Discussion on Possible Mechanisms and Their Therapeutic Potential

Author(s): Amy Bishop, Neil R. Cashman

Journal Name: Current Drug Metabolism

Volume 4 , Issue 2 , 2003

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The free radical, nitric oxide (NO), is synthesized by mammalian cells and is utilized for normal cellular functions. High levels of NO are released during disease, injury and inflammation. NO at high concentrations more readily combines with other oxidants to form reactive nitrogenous species (RNS), which can wreak havoc on the cell by damaging a variety of cellular targets, such as DNA and proteins, ultimately leading to apoptosis, mutagenesis or carcinogenesis. Cells have natural resistance mechanisms to nitrooxidative stress that are either defective (as can occur in disease), or overwhelmed (as can occur in injury and inflammation). It has been found recently in the CNS that resistance to normally toxic levels of NO can be induced by nontoxic levels of NO and that this induction is correlated with and dependent upon increased levels and activity of the heme-metabolizing enzyme, heme oxygenase-1 (HO-1). HO1- mediated metabolism of heme groups released from NO-damaged proteins leads to a change in the levels of redox-active iron and a release of carbon monoxide (CO) and bilirubin, all of which have been implicated in cellular resistance to oxidative stress. Perhaps one or more of the products of HO1 heme metabolism is involved in induced adaptive resistance or perhaps a heme-independent mechanism is involved. In fact, a variety of possible mechanisms may be involved in induced resistance to NO in the CNS. Ultimately elucidating these mechanisms will enable us to modulate them for therapeutic potential.

Keywords: Oxidative Stress, nitric oxide, apoptosis, carcinogenesis, heme oxygenase-1

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Article Details

Year: 2003
Published on: 01 March, 2012
Page: [171 - 184]
Pages: 14
DOI: 10.2174/1389200033489514
Price: $65

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