Prevention of mitochondrial injury by manganese superoxide dismutase reveals a primary mechanism for alkaline-induced cell death

Hideyuki J. Majima, Terry D. Oberley, Katsutoshi Furukawa, Mark P. Mattson, Hsiu Chuan Yen, Luke I. Szweda, Daret K. St. Clair

Research output: Contribution to journalArticle

Abstract

Alkalosis is a clinical complication resulting from various pathological and physiological conditions. Although it is well established that reducing the cellular proton concentration is lethal, the mechanism leading to cell death is unknown. Mitochondrial respiration generates a proton gradient and superoxide radicals, suggesting a possible link between oxidative stress, mitochondrial integrity, and alkaline-induced cell death. Manganese superoxide dismutase removes superoxide radicals in mitochondria, and thus protects mitochondria from oxidative injury. Cells cultured under alkaline conditions were found to exhibit elevated levels of mitochondrial membrane potential, reactive oxygen species, and calcium which was accompanied by mitochondrial damage, DNA fragmentation, and cell death. Overexpression of manganese superoxide dismutase reduced the levels of intracellular reactive oxygen species and calcium, restored mitochondrial transmembrane potential, and prevented cell death. The results suggest that mitochondria are the primary target for alkaline-induced cell death and that free radical generation is an important and early event conveying cell death signals under alkaline conditions.

Original languageEnglish (US)
Pages (from-to)8217-8224
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number14
DOIs
StatePublished - Apr 3 1998
Externally publishedYes

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Cell death
Superoxide Dismutase
Cell Death
Mitochondria
Wounds and Injuries
Superoxides
Protons
Reactive Oxygen Species
Calcium
Alkalosis
Oxidative stress
Mitochondrial Membrane Potential
Conveying
DNA Fragmentation
Mitochondrial DNA
Membrane Potentials
Free Radicals
Cultured Cells
Respiration
Oxidative Stress

ASJC Scopus subject areas

  • Biochemistry

Cite this

Majima, H. J., Oberley, T. D., Furukawa, K., Mattson, M. P., Yen, H. C., Szweda, L. I., & St. Clair, D. K. (1998). Prevention of mitochondrial injury by manganese superoxide dismutase reveals a primary mechanism for alkaline-induced cell death. Journal of Biological Chemistry, 273(14), 8217-8224. https://doi.org/10.1074/jbc.273.14.8217

Prevention of mitochondrial injury by manganese superoxide dismutase reveals a primary mechanism for alkaline-induced cell death. / Majima, Hideyuki J.; Oberley, Terry D.; Furukawa, Katsutoshi; Mattson, Mark P.; Yen, Hsiu Chuan; Szweda, Luke I.; St. Clair, Daret K.

In: Journal of Biological Chemistry, Vol. 273, No. 14, 03.04.1998, p. 8217-8224.

Research output: Contribution to journalArticle

Majima, HJ, Oberley, TD, Furukawa, K, Mattson, MP, Yen, HC, Szweda, LI & St. Clair, DK 1998, 'Prevention of mitochondrial injury by manganese superoxide dismutase reveals a primary mechanism for alkaline-induced cell death', Journal of Biological Chemistry, vol. 273, no. 14, pp. 8217-8224. https://doi.org/10.1074/jbc.273.14.8217
Majima, Hideyuki J. ; Oberley, Terry D. ; Furukawa, Katsutoshi ; Mattson, Mark P. ; Yen, Hsiu Chuan ; Szweda, Luke I. ; St. Clair, Daret K. / Prevention of mitochondrial injury by manganese superoxide dismutase reveals a primary mechanism for alkaline-induced cell death. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 14. pp. 8217-8224.
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