Membrane "Lens" Effect: Focusing the Formation of Reactive Nitrogen Oxides from the NO/O2 Reaction
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- 作者：Matias N. Mö ; ller ; Qian Li ; Dario A. Vitturi ; John M. Robinson ; Jack R. Lancaster ; Jr. ; Ana Denicola
- 刊名：Chemical Research in Toxicology
- 出版年：2007
- 出版时间：April 2007
- 年：2007
- 卷：20
- 期：4
- 页码：709 - 714
- 全文大小：255K
- 年卷期：v.20,no.4(April 2007)
- ISSN：1520-5010
文摘
It was previously observed that lipid membranes accelerate 
NO disappearance (Liu et al. (1998) Proc.Natl. Acad. Sci. U.S.A. 95, 2175), and here, we demonstrate that this translates into increased rates ofNO2 production and nitrosative chemistry. Not only the phospholipid membranes but also theatherosclerosis-related low-density lipoprotein (LDL) were able to accelerate the formation of NO2, studiedby stopped-flow spectrophotometry using ABTS as a probe. In addition, membranes, LDL, and TritonX-100 micelles significantly accelerated S-nitrosation of glutathione and captopril. It is shown here thatautoxidation of NO occurs 30 times more rapidly within the hydrophobic interior of these particles thanin an equal volume of water, approximately 1 order of magnitude less than previous reports. Thisacceleration can be explained by the ~3 times higher solubility of NO and O2 into these hydrophobicphases relative to water, which results in a higher local concentration of reactants ("lens effect") and,therefore, a higher rate of reaction. It is predicted that 50% of the oxidizing and nitrosating speciesderived from NO autoxidation in cells will be formed in the small volume comprising cellular membranes(3% of the total); thus, biomolecules near the membranes will be exposed to fluxes of reactive nitrogenspecies 30-fold higher than their cytosolic counterparts.
NO disappearance (Liu et al. (1998) Proc.Natl. Acad. Sci. U.S.A. 95, 2175), and here, we demonstrate that this translates into increased rates ofNO2 production and nitrosative chemistry. Not only the phospholipid membranes but also theatherosclerosis-related low-density lipoprotein (LDL) were able to accelerate the formation of NO2, studiedby stopped-flow spectrophotometry using ABTS as a probe. In addition, membranes, LDL, and TritonX-100 micelles significantly accelerated S-nitrosation of glutathione and captopril. It is shown here thatautoxidation of NO occurs 30 times more rapidly within the hydrophobic interior of these particles thanin an equal volume of water, approximately 1 order of magnitude less than previous reports. Thisacceleration can be explained by the ~3 times higher solubility of NO and O2 into these hydrophobicphases relative to water, which results in a higher local concentration of reactants ("lens effect") and,therefore, a higher rate of reaction. It is predicted that 50% of the oxidizing and nitrosating speciesderived from NO autoxidation in cells will be formed in the small volume comprising cellular membranes(3% of the total); thus, biomolecules near the membranes will be exposed to fluxes of reactive nitrogenspecies 30-fold higher than their cytosolic counterparts.