Biological effects of menadione photochemistry: Effects of menadione on biological systems may not involve classical oxidant production

M. L. McCormick, G. M. Denning, K. J. Reszka, P. Bilski, G. R. Buettner, G. T. Rasmussen, M. A. Railsback, B. E. Britigan

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Because cell-mediated reduction of menadione leads to the generation of reactive oxygen species (ROS), this quinone is widely used to investigate the effects of ROS on cellular functions. We report that A549 human lung epithelial cells exposed to menadione demonstrate a dose-dependent increase in both intracellular calcium ([Ca2+](i)) and ROS formation. The concentrations of menadione required to initiate these two events are markedly different, with ROS detection requiring higher levels of menadione. Modulators of antioxidant defences (e.g. buthionine sulphoximine, 3-amino-1,2,4-triazole) have little effect on the [Ca2+](i) response to menadione, suggesting that ROS formation does not account for menadione-dependent alterations in [Ca2+](i). Additional evidence suggests that menadione photochemistry may be responsible for the observed [Ca2+](i) effects. Specifically: (a) EPR studies with the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) show that light exposure (maximum effect at 340 nm) stimulates menadione-dependent formation of the DMPO/OH spin adduct that was not sensitive to antioxidant interventions; (b) DMPO inhibits menadione and light-dependent increases in [Ca2+](i); and (c) light (maximum effect at 340 nm) augments the deleterious effects of menadione on cell viability as determined by 51Cr release. These photo effects do not appear to involve formation of singlet oxygen by menadione, but rather are the result of the oxidizing chemistry initiated by menadione in the triplet state. This work demonstrates that menadione species generated by photo-irradiation can exert biological effects on cellular functions and points to the potential importance of photochemistry in studies of menadione-mediated cell damage.

Original languageEnglish (US)
Pages (from-to)797-804
Number of pages8
JournalBiochemical Journal
Volume350
Issue number3
DOIs
StatePublished - Sep 15 2000

Fingerprint

Photochemistry
Vitamin K 3
Photochemical reactions
Biological systems
Oxidants
Reactive Oxygen Species
Light
Antioxidants
Cells
Amitrole
Buthionine Sulfoximine
Singlet Oxygen
Modulators

Keywords

  • A549 cells
  • Electron paramagnetic resonance
  • Free radical
  • Intracellular calcium
  • Singlet oxygen

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Biological effects of menadione photochemistry : Effects of menadione on biological systems may not involve classical oxidant production. / McCormick, M. L.; Denning, G. M.; Reszka, K. J.; Bilski, P.; Buettner, G. R.; Rasmussen, G. T.; Railsback, M. A.; Britigan, B. E.

In: Biochemical Journal, Vol. 350, No. 3, 15.09.2000, p. 797-804.

Research output: Contribution to journalArticle

McCormick, M. L. ; Denning, G. M. ; Reszka, K. J. ; Bilski, P. ; Buettner, G. R. ; Rasmussen, G. T. ; Railsback, M. A. ; Britigan, B. E. / Biological effects of menadione photochemistry : Effects of menadione on biological systems may not involve classical oxidant production. In: Biochemical Journal. 2000 ; Vol. 350, No. 3. pp. 797-804.
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AU - Reszka, K. J.

AU - Bilski, P.

AU - Buettner, G. R.

AU - Rasmussen, G. T.

AU - Railsback, M. A.

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