Metallothionein protects against the cytotoxic and DNA-damaging effects of nitric oxide.

Schwarz, MA; Lazo, J S; Yalowich, Jack C.; Allen, WP; Whitmore, Mark M; Bergonia, HA; Tzeng, Edith; Tr, Billiar; Robbins, P. D.; Lancaster, Jr Jr

doi:10.1073/pnas.92.10.4452

Cited by 232 publications

(126 citation statements)

References 47 publications

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“…We have shown a similar increase in DNIC formation in cells expressing increased levels of metallothionein which also induces resistance to SNAP toxicity and DNA damage [39], although mitochondrial function was not measured. However, at present we do not know the identity of the thiol ligands in the DNIC and whether these complexes play a causal role in protection.…”

Section: Discussionmentioning

confidence: 68%

Nitrogen oxide‐induced autoprotection in isolated rat hepatocytes

Kim

Bergonia

Lancaster³

1995

FEBS Letters

197

110

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Pretreatment of rat hepatocytes with low-dose nitrogen oxide (addition of SNAP in vitro or induction of nitric oxide synthase in vitro or in vivo) imparts resistance to killing and decrease in aconitase and mitochondrial electron transfer from a second exposure to a higher dose of SNAP. Induction of this resistance is prevented by cycloheximide, indicating upregulation of protective protein(s). Ferritin levels are increased as are nonheme iron-NO EPR signals. Tin-protoporphyrin (SnPP) prevents protection, suggesting involvement of hsp32 (heme oxygenase) and/or guanylyl cyclase (GC). Cross-resistance to H2Oz killing is also observed, which is also prevented by cycloheximide and SnPP. Thus, hepatocytes possess inducible protective mechanisms against nitrogen oxide and reactive oxygen toxicity.

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Section: Discussionmentioning

confidence: 68%

Nitrogen oxide‐induced autoprotection in isolated rat hepatocytes

Kim

Bergonia

Lancaster³

1995

FEBS Letters

197

110

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“…There are data to support a common role of MnSOD and metallothionein in the cellular response to chemical-induced or radiation-induced damage. 33,48,49 Recent data from one of these systems support the concept that overexpression before irradiation of an antioxidant gene that is naturally expressed at a lower level may be radioprotective in vivo. 49 Protection of the rodent lung from bleomycininduced fibrosis has been reported using a transgene approach.…”

Section: Discussionmentioning

confidence: 97%

“…33,48,49 Recent data from one of these systems support the concept that overexpression before irradiation of an antioxidant gene that is naturally expressed at a lower level may be radioprotective in vivo. 49 Protection of the rodent lung from bleomycininduced fibrosis has been reported using a transgene approach. 50 For irradiation protection, MnSOD overexpression is theoretically attractive as it does not push cells out of G 0 51 and has an advantage in this regard, especially for cells in the lung which may not be cycling during irradiation exposure.…”

Section: Discussionmentioning

confidence: 97%

Prevention of late effects of irradiation lung damage by manganese superoxide dismutase gene therapy

et al. 1998

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“…For overexpression in S2 cells, copper(II) sulfate was used to induce transcription from a metallothionein promoter in the plasmid construct. This induction would also be expected to induce expression of the endogenous metallothionein in S2 cells, which can protect these cells from some oxidative and nitrosative stresses [58,59] and potentially confound analyses of AsPrx-4783. Data in support of this hypothesis came from a preliminary experiment in which S2 cells were mock transfected and challenged with hydrogen peroxide or DEA-NO with or without copper(II) sulfate pretreatment.…”

Section: Discussionmentioning

confidence: 99%

A mosquito 2-Cys peroxiredoxin protects against nitrosative and oxidative stresses associated with malaria parasite infection

Peterson

Luckhart

2006

Free Radical Biology and Medicine

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Malaria parasite infection in anopheline mosquitoes induces nitrosative and oxidative stresses that limit parasite development, but also damage mosquito tissues in proximity to the response. Based on these observations, we proposed that cellular defenses in the mosquito may be induced to minimize self-damage. Specifically, we hypothesized that peroxiredoxins (Prxs), enzymes known to detoxify reactive oxygen species (ROS) and reactive nitrogen oxide species (RNOS), protect mosquito cells. We identified an Anopheles stephensi 2-Cys Prx ortholog of Drosophila melanogaster Prx-4783, which protects fly cells against oxidative stresses. To assess function, AsPrx-4783 was overexpressed in D. melanogaster (S2) and in A. stephensi (MSQ43) cells and silenced in MSQ43 cells with RNA interference before treatment with various ROS and RNOS. Our data revealed that AsPrx-4783 and DmPrx-4783 differ in host cell protection and that AsPrx-4783 protects A. stephensi cells against stresses that are relevant to malaria parasite infection in vivo, namely nitric oxide (NO), hydrogen peroxide, nitroxyl, and peroxynitrite. Further, AsPrx-4783 expression is induced in the mosquito midgut by parasite infection at times associated with peak nitrosative and oxidative stresses. Hence, whereas the NO-mediated defense response is toxic to both host and parasite, AsPrx-4783 may shift the balance in favor of the mosquito. KeywordsMalaria; Mosquito; Peroxiredoxin; Plasmodium; Anopheles; Nitric oxide; Nitrosative stress; Free radicals It has long been recognized that reactive oxygen species (ROS) and, more recently, reactive nitrogen oxide species (RNOS) function to defend hosts against pathogens [1]. Although ROS and RNOS are cytotoxic to pathogens and parasites, they also induce oxidative and nitrosative stresses in the host and can damage host tissues [1]. Host protection against oxidative and nitrosative stress, therefore, is vital for homeostasis and hence survival. Gene products that confer protection against ROS are well known. In contrast, gene products that confer protection against RNOS have been identified, but are less well studied. The peroxiredoxins (Prxs) are a recently discovered family of antioxidant peroxidases that can reduce hydrogen peroxide and alkyl hydroperoxides to water and the corresponding alcohols, respectively, and can protect cells from widely divergent organisms against a variety of nitrosative stress challenges [2][3][4][5][6].Prxs do not show sequence homology to other known antioxidant enzymes. Crystal structures of PrxI, II, V, and VI have revealed that Prxs are novel members of the thioredoxin fold * Corresponding author. Fax: +1 530 752 8692. E-mail address: sluckhart@ucdavis.edu (S. Luckhart). NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript superfamily [7,8]. Unlike most peroxidases-which contain a heme ring at their active site (e.g., cytochrome c peroxidase) or a redox-sensitive moiety like selenocysteine (glutathione peroxidase; GPx), vanadium (algal bro...

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Metallothionein protects against the cytotoxic and DNA-damaging effects of nitric oxide.

Cited by 232 publications

References 47 publications

Nitrogen oxide‐induced autoprotection in isolated rat hepatocytes

Nitrogen oxide‐induced autoprotection in isolated rat hepatocytes

Prevention of late effects of irradiation lung damage by manganese superoxide dismutase gene therapy

A mosquito 2-Cys peroxiredoxin protects against nitrosative and oxidative stresses associated with malaria parasite infection

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