Superoxide‐dependent formation of hydroxyl radicals from NADH and NADPH in the presence of iron salts

Rowley, David A.; Halliwell, Barry

doi:10.1016/0014-5793(82)80214-7

Cited by 84 publications

(24 citation statements)

References 13 publications

(18 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…-dependent degradation of hyaluronic acid to 50, 82, and 84%, respectively (Del Maestro et aI., 1979). In addition, OH· induced hydroxylation of aromatic compounds was decreased by about 50% with 10 mM mannitol (Hal liwell, 1978a;Rowley and Halliwell, 1982). It should be pointed out, however, that these values were obtained in aqueous systems.…”

Section: Mechanism Of Mitochondrial Damagementioning

confidence: 99%

Respiratory Activity of Isolated Rat Brain Mitochondria followingin vitroExposure to Oxygen Radicals

Hillered

Ernster

1983

J Cereb Blood Flow Metab

169

View full text Add to dashboard Cite

Summary: Respiratory activity of isolated rat brain mi tochondria was measured following in vitro exposure to oxygen radicals. The radicals were generated by hypoxanthine and xanthine oxidase in the presence of a suitable iron chelate and caused a severe inhibition of respiration stimulated by phosphate plus ADP (with ma late + glutamate as substrate). The damage could be pre vented by catalase or high concentrations of mannitol, but not by superoxide dismutase. A similar effect was ob served when hypoxanthine and xanthine oxidase were re-

show abstract

Section: Mechanism Of Mitochondrial Damagementioning

confidence: 99%

Respiratory Activity of Isolated Rat Brain Mitochondria followingin vitroExposure to Oxygen Radicals

Hillered

Ernster

1983

J Cereb Blood Flow Metab

169

View full text Add to dashboard Cite

show abstract

“…Both thiols (10 Ϫ3 M) and NAD(P)H (10 Ϫ3 M) (44,45) can transfer electrons to free iron in vitro and are far more abundant in vivo than is O 2 Ϫ . Free reduced flavins are also efficient reductants of iron, and in fact, their accumulation in respiration-inhibited cells causes a large increase in vulnerability to DNA damage (53).…”

mentioning

confidence: 99%

High Levels of Intracellular Cysteine Promote Oxidative DNA Damage by Driving the Fenton Reaction

2003

View full text Add to dashboard Cite

. However, when cells were cultured with poor sulfur sources and then exposed to cystine, they transiently exhibited a greatly increased susceptibility to H 2 O 2 , with <1% surviving the challenge. Cell death was due to an unusually rapid rate of DNA damage, as indicated by their filamentation, a high rate of mutation among the survivors, and DNA lesions by a direct assay. Cell-permeable iron chelators eliminated sensitivity, indicating that intracellular free iron mediated the conversion of H 2 O 2 into a hydroxyl radical, the direct effector of DNA damage. The cystine treatment caused a temporary loss of cysteine homeostasis, with intracellular pools increasing about eightfold. In vitro analysis demonstrated that cysteine reduces ferric iron with exceptional speed. This action permits free iron to redox cycle rapidly in the presence of H 2 O 2 , thereby augmenting the rate at which hydroxyl radicals are formed. During routine growth, cells maintain small cysteine pools, and cysteine is not a major contributor to DNA damage. Thus, the homeostatic control of cysteine levels is important in conferring resistance to oxidants. More generally, this study provides a new example of a situation in which the vulnerability of cells to oxidative DNA damage is strongly affected by their physiological state.

show abstract

“…These iron-mediated DNA damageinduced lesions seem to be repaired mainly by recombination (27,32). Even in the absence of oxygen, other intracellular reductants, such as NADH and glutathione, can damage DNA in vitro and in vivo in the presence of iron (8,23,35).…”

mentioning

confidence: 99%

Geobacter sulfurreducensHas Two AutoregulatedlexAGenes Whose Products Do Not Bind therecAPromoter: Differing Responses oflexAandrecAto DNA Damage

et al. 2003

View full text Add to dashboard Cite

The Escherichia coli LexA protein was used as a query sequence in TBLASTN searches to identify the lexA gene of the ␦-proteobacterium Geobacter sulfurreducens from its genome sequence. The results of the search indicated that G. sulfurreducens has two independent lexA genes designated lexA1 and lexA2. A copy of a dinB gene homologue, which in E. coli encodes DNA polymerase IV, is present downstream of each lexA gene. Reverse transcription-PCR analyses demonstrated that, in both cases, lexA and dinB constitute a single transcriptional unit. Electrophoretic mobility shift assays with purified LexA1 and LexA2 proteins have shown that both proteins bind the imperfect palindrome GGTTN 2 CN 4 GN 3 ACC found in the promoter region of both lexA1 and lexA2. This sequence is also present upstream of the Geobacter metallireducens lexA gene, indicating that it is the LexA box of this bacterial genus. This palindrome is not found upstream of either the G. sulfurreducens or the G. metallireducens recA genes. Furthermore, DNA damage induces expression of the lexA-dinB transcriptional unit but not that of the recA gene. However, the basal level of recA gene expression is dramatically higher than that of the lexA gene. Likewise, the promoters of the G. sulfurreducens recN, ruvAB, ssb, umuDC, uvrA, and uvrB genes do not contain the LexA box and are not likely to bind to the LexA1 or LexA2 proteins. G. sulfurreducens is the first bacterial species harboring a lexA gene for which a constitutive expression of its recA gene has been described.

show abstract

Superoxide‐dependent formation of hydroxyl radicals from NADH and NADPH in the presence of iron salts

Cited by 84 publications

References 13 publications

Respiratory Activity of Isolated Rat Brain Mitochondria followingin vitroExposure to Oxygen Radicals

Respiratory Activity of Isolated Rat Brain Mitochondria followingin vitroExposure to Oxygen Radicals

High Levels of Intracellular Cysteine Promote Oxidative DNA Damage by Driving the Fenton Reaction

Geobacter sulfurreducensHas Two AutoregulatedlexAGenes Whose Products Do Not Bind therecAPromoter: Differing Responses oflexAandrecAto DNA Damage

Contact Info

Product

Resources

About