Mitochondrial damage due to SOD1 deficiency in SH‐SY5Y neuroblastoma cells: a rationale for the redundancy of SOD1

Aquilano, Katia; Vigilanza, Paola; Rotilio, Giuseppe; Ciriolo, Maria Rosa

doi:10.1096/fj.05-5225fje

Cited by 54 publications

(43 citation statements)

References 46 publications

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“…All values obtained by QRT-PCR overlapped with the microarray data at the 95% confidence interval, validating the microarray data we have obtained for these five genes at all time points and mouse models. 2 …”

Section: Validation Of Microarray Resultsmentioning

confidence: 99%

“…The Srxn1 transcript was increased 2.3-fold, and sulfiredoxin protein was increased Ͼ6-fold. Mt1 transcript was increased 4.5-fold and Mt2 transcript was increased 3.6-fold (Supplemental Table S1), but the Mt2 data did not reach the statistical cutoff (P Ͻ 0.0083 vs. P Ͻ 0.005); the protein levels of metallothionein 1 ϩ 2 are increased 4.5-fold (Mt1 and Mt2 have the same molecular 2 For an extensive comparison of microarray vs. "true" fold changes see Tables 2 and 3 Genes showing a significant difference of Ͼ1.5-fold when we compared untreated WT mice with either WT mice treated with diquat (DQ) or untreated Gpx1 Ϫ/Ϫ and Sod1 Ϫ/Ϫ mice are shown. Duplicates (by gene name or unigene ID) were removed.…”

Section: Confirmation Of Selected Transcripts At the Protein Levelmentioning

confidence: 99%

“…The upregulation of so many components of the thiol antioxidant system in the Sod1 Ϫ/Ϫ liver could be physiologically protective because free thiols react with superoxide at ϳ10 3 -10 4 M Ϫ1 s Ϫ1 (9,87), thereby scavenging the excess superoxide in the absence of CuZn-SOD. Thiol antioxidants, e.g., glutathione, N-acetylcysteine, cysteine, and metallothionein, can rescue Sod1 Ϫ/Ϫ yeast (80,94), and elevated glutathione biosynthesis rescues neuroblastoma cells in which CuZn-SOD was knocked down by RNA interference (2). Of the antioxidant genes upregulated in the Sod1 Ϫ/Ϫ mice listed in Table 4, none was statistically significantly altered in the Gpx1 Ϫ/Ϫ mice, which exhibit no significant elevation in oxidative damage in the absence of exogenous oxidative stressors.…”

Section: Gpx1mentioning

confidence: 99%

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The in vivo gene expression signature of oxidative stress

Han

Muller

Pérez

et al. 2008

Physiological Genomics

217

155

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Section: Validation Of Microarray Resultsmentioning

confidence: 99%

Section: Confirmation Of Selected Transcripts At the Protein Levelmentioning

confidence: 99%

Section: Gpx1mentioning

confidence: 99%

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The in vivo gene expression signature of oxidative stress

Han

Muller

Pérez

et al. 2008

Physiological Genomics

217

155

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“…43 Some reports showed that ROS generation during mitochondria-dependent apoptosis occurs downstream of the release of mitochondrial proapoptotic factors to cytosol. 44 In many apoptosis models, however, ROS act as upstream signaling molecules that initiate cell death.…”

Section: Discussionmentioning

confidence: 99%

Single-cell analysis of dihydroartemisinin–induced apoptosis through reactive oxygen species–mediated caspase-8 activation and mitochondrial pathway in ASTC-a-1 cells using fluorescence imaging techniques

et al. 2010

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Abstract. Dihydroartemisinin ͑DHA͒, a front-line antimalarial herbal compound, has been shown to possess promising anticancer activity with low toxicity. We have previously reported that DHA induced caspase-3-dependent apoptosis in human lung adenocarcinoma cells. However, the cellular target and molecular mechanism of DHAinduced apoptosis is still poorly defined. We use confocal fluorescence microscopy imaging, fluorescence resonance energy transfer, and fluorescence recovery after photobleaching techniques to explore the roles of DHA-elicited reactive oxygen species ͑ROS͒ in the DHAinduced Bcl-2 family proteins activation, mitochondrial dysfunction, caspase cascade, and cell death. Cell Counting Kit-8 assay and flow cytometry analysis showed that DHA induced ROS-mediated apoptosis. Confocal imaging analysis in a single living cell and Western blot assay showed that DHA triggered ROS-dependent Bax translocation, mitochondrial membrane depolarization, alteration of mitochondrial morphology, cytochrome c release, caspase-9, caspase-8, and caspase-3 activation, indicating the coexistence of ROS-mediated mitochondrial and death receptor pathway. Collectively, our findings demonstrate for the first time that DHA induces cell apoptosis by triggering ROS-mediated caspase-8/Bid activation and the mitochondrial pathway, which provides some novel insights into the application of DHA as a potential anticancer drug and a new therapeutic strategy by targeting ROS signaling in lung adenocarcinoma therapy in the future.

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“…2c) have decreased activity of SOD2. Although the role of SOD2 appears to be intrinsic for cellular survival, cytoplasmic copper/zinc SOD (SOD1) is far more abundant in the cell, accounting for 90% of the total SOD activity (18,19). Thus, we tested the protein expression of SOD1 in GILT Ϫ/Ϫ and GILT WT fibroblast cell line and primary fibroblasts (Fig.…”

Section: Gilt-deficient Mouse Fibroblasts Show Increased Proliferatiomentioning

confidence: 99%

An Unexpected Functional Link between Lysosomal Thiol Reductase and Mitochondrial Manganese Superoxide Dismutase

Bogunovic

Stojakovic

Chen

et al. 2008

Journal of Biological Chemistry

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Gamma interferon-inducible thiol reductase (GILT) is an enzyme involved in the initial steps of antigen processing and presentation. Recently we have shown that GILT is also expressed in mouse T cells, where it exerts an inhibitory role on T cell activation. In this study, we identified mitochondrial manganese superoxide dismutase (SOD2) as one of the key intermediaries affected by GILT expression in fibroblasts. Expression and activity of SOD2 is reduced in the absence of GILT because of reduced SOD2 protein stability. The forced increase in SOD2 expression in the absence of GILT restores fibroblast proliferation to wild-type levels. Thus, GILT appears to have a fundamental role in cellular proliferation mediated through its influence on SOD2 protein activity and expression.Enzymes of the thiol reductase family carry out reduction, oxidation, and isomerization of protein disulfide bonds in cytosol (for example, thioredoxin) (1, 2), mitochondria (3), endoplasmic reticulum (protein-disulfide isomerase) (2), and lysosomes (gamma interferon-inducible thiol reductase, GILT).2 The majority of these enzymes are functional at neutral or slightly alkaline conditions (4), they have similar three-dimensional structures, and all feature a conservative active site loop containing two cysteines in the sequence -CGPC-(5). GILT is a unique and unusual member of the thiol reductase family because its optimal enzymatic activity is at a low pH (4.5-5.5) (6 -8) and has an atypical active site (-CGAC-).GILT is synthesized as a 35-kDa soluble glycoprotein precursor and is transported to the endosomal compartment via the mannose-6-P receptor pathway (9). It is processed into the mature form (30 kDa) by proteolytic removal of N-and C-terminal peptides. The protein has an approximate molecular mass of 30 kDa and was therefore initially named IP-30 (6). In addition to endosomal/lysosomal localization, GILT is secreted in the tissue culture medium of the GILT-expressing cell lines (7,10), and is present in mouse sera.3 GILT is constitutively expressed in professional antigen-presenting cells (APCs), but it is also inducible by pro-inflammatory cytokines such as interferon ␥, tumor necrosis factor ␣, and interleukin 1␤ (9).Using GILT Ϫ/Ϫ mice as a model, we have shown that GILT catalyzes initial unfolding of antigenic protein (protein becomes more accessible for further processing by cathepsins) and therefore facilitates protein/peptide binding to MHC class II molecules (10). By changing the redox state of exogenous antigenic proteins with disulfide bonds, GILT initiates the adaptive immune response. However, we have shown that GILT is constitutively expressed in T cells and has a role in the regulation of T cell activation. This is so far the only known GILT function not related to MHC class II processing (11). GILT Ϫ/Ϫ T cells show increased proliferation and cytotoxic T cell activity in response to anti-CD3 stimulation. This observation suggests that GILT has a more fundamental role in cellular processes than just reduction of antigens...

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Mitochondrial damage due to SOD1 deficiency in SH‐SY5Y neuroblastoma cells: a rationale for the redundancy of SOD1

Cited by 54 publications

References 46 publications

The in vivo gene expression signature of oxidative stress

The in vivo gene expression signature of oxidative stress

Single-cell analysis of dihydroartemisinin–induced apoptosis through reactive oxygen species–mediated caspase-8 activation and mitochondrial pathway in ASTC-a-1 cells using fluorescence imaging techniques

An Unexpected Functional Link between Lysosomal Thiol Reductase and Mitochondrial Manganese Superoxide Dismutase

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