Down regulation of DJ-1 enhances cell death by oxidative stress, ER stress, and proteasome inhibition

Yokota, Takanori; Sugawara, Kazuki; Ito, Kei; Takahashi, Ryōsuke; Ariga, Hiroyoshi; Mizusawa, Hidehiro

doi:10.1016/j.bbrc.2003.11.056

Cited by 344 publications

(274 citation statements)

References 20 publications

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“…Studies in cell culture and animal models suggest that DJ-1 protein responds to oxidative stress (23)(24)(25)(26)(27)(28)(29)(30)(31)(32), shifting to more acidic species (33,34). This includes oxidation of highly conserved cysteine residues, leading to the formation of cysteine sulfinic or sulfonic acids (35,36).…”

mentioning

confidence: 99%

Mutational analysis of DJ-1 in Drosophila implicates functional inactivation by oxidative damage and aging

Meulener

Xu²,

Thomson³

et al. 2006

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

224

191

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Inherited mutations in PARK7 , the gene encoding DJ-1, are associated with loss of protein function and early-onset parkinsonism. Like human DJ-1 (hDJ-1), Drosophila DJ-1b protects against oxidative insult and is modified with oxidation. We demonstrate that hDJ-1 rescues flies mutant for DJ-1b, and that a conserved cysteine residue in the fly protein (C104, analogous to C106 in hDJ-1) is critical for biological antioxidant function in vivo . Targeted mutagenesis suggests that modification of DJ-1b at this residue inactivates the protective activity of the protein against oxidative stress. Further studies show that DJ-1 modification increases dramatically with age in flies, mice, and humans, with aged flies showing strikingly increased susceptibility to oxidative stress and markedly enhanced DJ-1b modification upon oxidative challenge. Overoxidation of DJ-1 with age and exposure to oxidative toxins may lead to inactivation of DJ-1 function, suggesting a role in susceptibility to sporadic Parkinson’s disease.

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mentioning

confidence: 99%

Mutational analysis of DJ-1 in Drosophila implicates functional inactivation by oxidative damage and aging

Meulener

Xu²,

Thomson³

et al. 2006

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

224

191

View full text Add to dashboard Cite

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“…This possibility was corroborated by proteomic profiling of treated cells revealing the expression of several proteins associated with the oxidative stress response and antioxidant activities in both cell lines. For example, maspin (40) and ferritin heavy chain (41) were induced in HCT 116, whereas transaldolase 1 (42), oncogene DJ1 (43), and lactotransferrin (44) were up-regulated in SW620. Similarly, the antitumor effect of another catalytic inhibitor of topoisomerase II, namely aclarubicin, which is strong DNA-intercalating agent as well, has been correlated with the generation of reactive oxygen species (45).…”

Section: Discussionmentioning

confidence: 99%

Differential antiproliferative mechanisms of novel derivative of benzimidazo[1,2-α]quinoline in colon cancer cells depending on their p53 status

Sedić¹,

Poznic²,

Gehrig³

et al. 2008

Molecular Cancer Therapeutics

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In the present article, we describe a mechanistic study of a novel derivative of N-amidino-substituted benzimidazo [1,2-A]quinoline in two human colorectal cancer cell lines differing in p53 gene status. We used a proteomic approach based on two-dimensional gel electrophoresis coupled with mass spectrometry to complement the results obtained by common molecular biology methods for analyzing cell proliferation, cell cycle, and apoptosis.

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“…In addition, decreased Park7 levels were detected in cerebrospinal fluid of late-onset PD patients (age > 50) compared with health controls [13]. Oxidative stress has been implicated in the pathogenesis of PD, because neuronal cells with either Park7 deletion or Park7 downregulation are sensitive to oxidative stress [14,15]. Given the antioxidant feature of Park7 and that oxidative stress is tightly related to inflammatory responses and survival in experimental sepsis [12,16], we hypothesized that Park7 protects against sepsis by modulating the cellular redox state.…”

Section: Introductionmentioning

confidence: 96%

Park7 interacts with p47phox to direct NADPH oxidase-dependent ROS production and protect against sepsis

Liu

Chen

et al. 2015

Cell Res

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Inappropriate inflammation responses contribute to mortality during sepsis. Through Toll-like receptors (TLRs), reactive oxygen species (ROS) produced by NADPH oxidase could modulate the inflammation responses. Parkinson disease (autosomal recessive, early onset) 7 (Park7) has a cytoprotective role by eliminating ROS. However, whether Park7 could modulate inflammation responses and mortality in sepsis is unclear. Here, we show that, compared with wild-type mice, Park7 −/− mice had significantly increased mortality and bacterial burdens in sepsis model along with markedly decreased systemic and local inflammation, and drastically impaired macrophage phagocytosis and bacterial killing abilities. Surprisingly, LPS and phorbol-12-myristate-13-acetate stimulation failed to induce ROS and proinflammatory cytokine production in Park7 −/− macrophages and Park7-deficient RAW264.7 cells. Through its C-terminus, Park7 binds to p47 phox , a subunit of the NADPH oxidase, to promote NADPH oxidase-dependent production of ROS. Restoration of Park7 expression rescues ROS production and improves survival in LPS-induced sepsis. Together, our study shows that Park7 has a protective role against sepsis by controlling macrophage activation, NA-DPH oxidase activation and inflammation responses.

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Down regulation of DJ-1 enhances cell death by oxidative stress, ER stress, and proteasome inhibition

Cited by 344 publications

References 20 publications

Mutational analysis of DJ-1 in Drosophila implicates functional inactivation by oxidative damage and aging

Mutational analysis of DJ-1 in Drosophila implicates functional inactivation by oxidative damage and aging

Differential antiproliferative mechanisms of novel derivative of benzimidazo[1,2-α]quinoline in colon cancer cells depending on their p53 status

Park7 interacts with p47phox to direct NADPH oxidase-dependent ROS production and protect against sepsis

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