Induction of the mitochondrial permeability transition by peroxynitrite

Packer, Michael A.; Scarlett, Jared L.; Martin, Stephen; Murphy, Michael P.

doi:10.1042/bst0250909

Cited by 59 publications

(28 citation statements)

References 19 publications

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“…PT induction also seems to be involved in releasing the apoptotic initiation factors, cytochrome c and Apaf-1, which activate downstream caspases, leading to apoptosis (Kluck et al, 1997;Scarlett and Murphy, 1997). Various reactive species, such as free radicals, ROS, and aldehydes, are known to activate the mitochondrial PT (Kristal et al, 1996;Packer et al, 1997). DOPAL and DOPEGAL, both of which are TOXICITY AND METABOLISM OF DOPAL AND DOPEGAL: ROLE OF ALDH generated by MAO on the outer mitochondrial membrane in close proximity to mitochondrial PT pores, have been reported to induce the Ca 2ϩ -mediated activation of the mitochondrial PT (Burke et al, 1998;Kristal et al, 2001).…”

Section: E Mechanisms Of Apoptosismentioning

confidence: 99%

Neurotoxicity and Metabolism of the Catecholamine-Derived 3,4-Dihydroxyphenylacetaldehyde and 3,4-Dihydroxyphenylglycolaldehyde: The Role of Aldehyde Dehydrogenase

2007

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Section: E Mechanisms Of Apoptosismentioning

confidence: 99%

Neurotoxicity and Metabolism of the Catecholamine-Derived 3,4-Dihydroxyphenylacetaldehyde and 3,4-Dihydroxyphenylglycolaldehyde: The Role of Aldehyde Dehydrogenase

2007

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“…These effects include lipid peroxidation, 8 protein nitration and nitrosylation, 9 DNA damage 10 and oxidation of thiols, 11 and are thought to result in mitochondrial dysfunction and cytotoxicity. [12][13][14][15] Since peroxynitrite very rapidly decomposes at physiological pH values, 16 its effects on target biomolecules should then be produced within a few seconds after addition to cultured cells, i.e., the time required for its disappearance from the intra-extracellular media.…”

Section: Introductionmentioning

confidence: 99%

Hydrogen peroxide generated at the level of mitochondria in response to peroxynitrite promotes U937 cell death via inhibition of the cytoprotective signalling mediated by cytosolic phospholipase A2

et al. 2004

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We have studied the relationships existing between delayed formation of H 2 O 2 and activation of cytosolic phospholipase A 2 (cPLA 2 ), events respectively promoting toxicity or survival in U937 cells exposed to peroxynitrite. The outcome of an array of different approaches using phospholipase A 2 inhibitors, or cPLA 2 antisense oligonucleotides, as well as specific respiratory chain inhibitors and respiration-deficient cells led to the demonstration that H 2 O 2 does not mediate toxicity by producing direct molecular damage. Rather, the effects of H 2 O 2 were found to be upstream to the arachidonic acid (AA)-mediated cytoprotective signalling and in fact causally linked to inhibition of cPLA 2 . Thus, it appears that U937 cells exposed to nontoxic concentrations of peroxynitrite are nevertheless committed to death, which however is normally prevented by the activation of parallel pathways resulting in cPLA 2 -dependent release of AA. A rapid necrotic response, however, takes place when high concentrations of peroxynitrite promote formation of H 2 O 2 at levels impairing the cPLA 2 cytoprotective signalling.

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“…As a strong oxidant, ONOO − reacts with protein and non-protein thiol residues [3], inhibits some enzymes of the mitochondrial electron transport chain [4], promotes lipid peroxidation [5] and DNA damage [6] and finally leads to mitochondrial permeability transition and cell death [7]. Thus many defence mechanisms have evolved to limit the levels and\or deleterious effects of ONOO − in biological systems [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Intracellular ascorbic acid enhances the DNA single-strand breakage and toxicity induced by peroxynitrite in U937 cells

et al. 2001

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A well-established protocol to increase the intracellular content of ascorbic acid was used to investigate the effects of the vitamin on DNA single-strand breakage and toxicity mediated by authentic peroxynitrite (ONOO-) in U937 cells. This protocol involved exposure for 60 min to 100 muM dehydroascorbic acid, which was taken up by the cells and converted into ascorbic acid via a GSH-independent mechanism. At the time of exposure to ONOO-, which was performed in fresh saline immediately after loading with dehydroascorbic acid, the vitamin present in the cells was all in its reduced form. It was found that, in cells that are otherwise ascorbate-deficient, an increase in their ascorbic acid content does not prevent, but rather enhances, the DNA-damaging and lethal responses mediated by exogenous ONOO-. These results therefore suggest that acute supplementation of ascorbic acid can be detrimental for individuals with pathologies associated with a decrease in ascorbic acid and in which ONOO- is known to promote deleterious effects

show abstract

Induction of the mitochondrial permeability transition by peroxynitrite

Abstract: and a-band regions of the spectrum, this species is more similar to 0 than to F. This may be considered a weakness of the mechanism.

Cited by 59 publications

References 19 publications

Neurotoxicity and Metabolism of the Catecholamine-Derived 3,4-Dihydroxyphenylacetaldehyde and 3,4-Dihydroxyphenylglycolaldehyde: The Role of Aldehyde Dehydrogenase

Neurotoxicity and Metabolism of the Catecholamine-Derived 3,4-Dihydroxyphenylacetaldehyde and 3,4-Dihydroxyphenylglycolaldehyde: The Role of Aldehyde Dehydrogenase

Hydrogen peroxide generated at the level of mitochondria in response to peroxynitrite promotes U937 cell death via inhibition of the cytoprotective signalling mediated by cytosolic phospholipase A2

Intracellular ascorbic acid enhances the DNA single-strand breakage and toxicity induced by peroxynitrite in U937 cells

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