Distinct Promoters Determine Alternative Transcription of gpx-4 into Phospholipid-Hydroperoxide Glutathione Peroxidase Variants

Maiorino, Matilde; Scapin, Margherita; Ursini, Fulvio; Biasolo, Maria Angela; Bosello, Valentina; Flohé, Leopold

doi:10.1074/jbc.m305327200

Cited by 112 publications

(71 citation statements)

References 40 publications

(52 reference statements)

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“…MdesPHGPX-2 showed greatest amino acid similarity (66%, 9e-57) with an Anopheles gambiae (EAA44749) PHGPX. The deduced protein sequences for both the Hessian fly PHGPXs revealed the presence of a conserved catalytic triad cysteine (C), glutamine (Q), and tryptophan (W) (3,6). The deduced catalytic triads for MdesPHGPX-1 and MdesPHGPX-2 were C47-Q78-W137 and C44-Q75-W134, respectively.…”

Section: Resultsmentioning

confidence: 99%

Antioxidant defense response in a galling insect

Mittapalli¹,

Neal²,

Shukle

2007

Proc. Natl. Acad. Sci. U.S.A.

107

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Herbivorous insect species are constantly challenged with reactive oxygen species (ROS) generated from endogenous and exogenous sources. ROS produced within insects because of stress and prooxidant allelochemicals produced by host plants in response to herbivory require a complex mode of antioxidant defense during insect/plant interactions. Some insect herbivores have a midgutbased defense against the suite of ROS encountered. Because the Hessian fly (Mayetiola destructor) is the major insect pest of wheat worldwide, and an emerging model for all gall midges, we investigated its antioxidant responses during interaction with its host plant. Quantitative data for two phospholipid glutathione peroxidases (MdesPHGPX-1 and MdesPHGPX-2), two catalases (MdesCAT-1 and MdesCAT-2), and two superoxide dismutases (MdesSOD-1 and MdesSOD-2) revealed high levels of all of the mRNAs in the midgut of larvae on susceptible wheat (compatible interaction). During development of the Hessian fly on susceptible wheat, a differential expression pattern was observed for all six genes. Analysis of larvae on resistant wheat (incompatible interaction) compared with larvae on susceptible wheat showed increased levels of mRNAs in larvae on resistant wheat for all of the antioxidant genes except MdesSOD-1 and MdesSOD-2. We postulate that the increased mRNA levels of MdesPHGPX-1, MdesPH-GPX-2, MdesCAT-1, and MdesCAT-2 reflect responses to ROS encountered by larvae while feeding on resistant wheat seedlings and/or ROS generated endogenously in larvae because of stress/ starvation. These results provide an opportunity to understand the cooperative antioxidant defense responses in the Hessian fly/ wheat interaction and may be applicable to other insect/plant interactions.Hessian fly ͉ insect/plant interaction ͉ reactive oxygen species ͉ wheat

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Section: Resultsmentioning

confidence: 99%

Antioxidant defense response in a galling insect

Mittapalli¹,

Neal²,

Shukle

2007

Proc. Natl. Acad. Sci. U.S.A.

107

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“…Several mechanisms of transcriptional regulation Maiorino et al 2003) have been suggested for various GPx4-isoforms, but cell activation studies (Kuhn and Borchert 2002;Tramer et al 2002;Sneddon et al 2003) and nonsense-mediated decay experiments (Sun et al 2001;Muller et al 2003) suggested additional post-transcriptional elements. Besides GPx4, other enzymes involved in eicosanoid metabolism such as 15-lipoxygen- …”

Section: Discussionmentioning

confidence: 99%

Translational regulation of glutathione peroxidase 4 expression through guanine-rich sequence-binding factor 1 is essential for embryonic brain development

Ufer

Wang²,

Fähling³

et al. 2008

Genes Dev.

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Phospholipid hydroperoxide glutathione peroxidase (GPx4) is a moonlighting selenoprotein, which has been implicated in basic cell functions such as anti-oxidative defense, apoptosis, and gene expression regulation. GPx4-null mice die in utero at midgestation, and developmental retardation of the brain appears to play a major role. We investigated post-transcriptional mechanisms of GPx4 expression regulation and found that the guanine-rich sequence-binding factor 1 (Grsf1) up-regulates GPx4 expression. Grsf1 binds to a defined target sequence in the 5-untranslated region (UTR) of the mitochondrial GPx4 (m-GPx4) mRNA, up-regulates UTR-dependent reporter gene expression, recruits m-GPx4 mRNA to translationally active polysome fractions, and coimmunoprecipitates with GPx4 mRNA. During embryonic brain development, Grsf1 and m-GPx4 are coexpressed, and functional knockdown (siRNA) of Grsf1 prevents embryonic GPx4 expression. When compared with mock controls, Grsf1 knockdown embryos showed significant signs of developmental retardations that are paralleled by apoptotic alterations (TUNEL staining) and massive lipid peroxidation (isoprostane formation). Overexpression of m-GPx4 prevented the apoptotic alterations in Grsf1-deficient embryos and rescued them from developmental retardation. These data indicate that Grsf1 up-regulates translation of GPx4 mRNA and implicate the two proteins in embryonic brain development.[Keywords: Glutathione peroxidase 4; guanine-rich sequence-binding factor 1; apoptosis; brain development; embryogenesis] Supplemental material is available at http://www.genesdev.org.

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“…The promoter regulating both forms of PHGPx contains a functional NF-Y site (32,59) and SP1/SP3 and members of the SMAD family binding sites (59). An alternative promoter lies in the first intron of the PHGPx gene, which guides the expression of the nuclear form of PHGPx (40,42). It contains binding sites for EGR1 and SREBP1 (7).…”

Section: Discussionmentioning

confidence: 99%

The GI-GPx Gene Is a Target for Nrf2

Banning

Deubel

Kluth

et al. 2005

Molecular and Cellular Biology

297

115

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The gastrointestinal glutathione peroxidase (GI-GPx, GPx2) is a selenoprotein that was suggested to act as barrier against hydroperoxide absorption but has also been implicated in the control of inflammation and malignant growth. In CaCo-2 cells, GI-GPx was induced by t-butyl hydroquinone (tBHQ) and sulforaphane (SFN), i.e., "antioxidants" known to activate the "antioxidant response element" (ARE) via electrophilic thiol modification of Keap1 in the Nrf2/Keap1 system. The functional significance of a putative ARE in the GI-GPx promoter was validated by transcriptional activation of reporter gene constructs upon exposure to electrophiles (tBHQ, SFN, and curcumin) or overexpression of Nrf2 and by reversal of these effects by mutation of the ARE in the promoter and by overexpressed Keap1. Binding of Nrf2 to the ARE sequence in authentic gpx2 was corroborated by chromatin immunoprecipitation. Thus, the presumed natural antioxidants sulforaphane and curcumin may exert their anti-inflammatory and anticarcinogenic effects not only by induction of phase 2 enzymes but also by the up-regulation of the selenoprotein GI-GPx.

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Distinct Promoters Determine Alternative Transcription of gpx-4 into Phospholipid-Hydroperoxide Glutathione Peroxidase Variants

Cited by 112 publications

References 40 publications

Antioxidant defense response in a galling insect

Antioxidant defense response in a galling insect

Translational regulation of glutathione peroxidase 4 expression through guanine-rich sequence-binding factor 1 is essential for embryonic brain development

The GI-GPx Gene Is a Target for Nrf2

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