Faculty Collaboration Database

Merocyanine 540-sensitized photokilling of leukemia cells: role of post-irradiation chain peroxidation of plasma membrane lipids as revealed by nitric oxide protection. Biochim Biophys Acta 2005 Feb 11;1722(1):51-9

Date

02/18/2005

Pubmed ID

15716134

DOI

10.1016/j.bbagen.2004.11.007

Scopus ID

2-s2.0-13544272674 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

The lipophilic dye merocyanine 540 (MC540) localizes primarily in the plasma membrane (PM) of tumor cells, where it can sensitize lethal photoperoxidative damage of potential therapeutic importance. We postulated (i) that chain peroxidation triggered by iron-catalyzed turnover of nascent hydroperoxides (LOOHs) generated by singlet oxygen ((1)O(2)) attack on PM lipids contributes significantly to overall cytolethality, and (ii) that nitric oxide (NO), a known scavenger of organic free radicals, would suppress this and, thus, act cytoprotectively. In accordance, irradiation of MC540-sensitized L1210 cells produced 5alpha-OOH, a definitive (1)O(2) adduct of PM cholesterol, which decayed during subsequent dark incubation with appearance of other signature peroxides, viz. free-radical-derived 7alpha/beta-OOH. Whereas chemical donor (SPNO or SNAP)-derived NO had little or no effect on post-irradiation 5alpha-OOH disappearance, it dose-dependently inhibited 7alpha/beta-OOH accumulation, consistent with interception of chain-carrying radicals arising from one-electron reduction of primary LOOHs. Using [(14)C]cholesterol as an L1210 PM probe, we detected additional after-light products of chain peroxidation, including diols (7alpha-OH, 7beta-OH) and 5,6-epoxides, the yields of which were enhanced by iron supplementation, but strongly suppressed by NO. Correspondingly, photoinitiated cell killing was significantly inhibited by NO introduced either immediately before or after light exposure. These findings indicate that prooxidant LOOH turnover plays an important role in photokilling and that NO, by intercepting propagating radicals, can significantly enhance cellular resistance.

Author List

Zareba M, Niziolek M, Korytowski W, Girotti AW

Author

Albert W. Girotti PhD Adjunct Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Line, Tumor
Cell Survival
Iron
Leukemia
Lipid Peroxidation
Membrane Lipids
Mice
Nitric Oxide
Oxidation-Reduction
Photochemotherapy
Photosensitizing Agents
Pyrimidinones