Oxidative insults induce DJ-1 upregulation and redistribution: Implications for neuroprotection

Lev, Nirit; Ickowicz, Debby; Melamed, Eldad; Offen, Daniel

doi:10.1016/j.neuro.2008.01.007

Cited by 123 publications

(97 citation statements)

References 26 publications

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“…Knockdown of DJͲ1 by siRNA in SHͲSY5Y human neuroblastoma cell line, enhanced susceptibility to several oxidative insults, including H 2 O 2 , MPP + and 6ͲOHDA [270]. Reciprocally, DJͲ1 overexpression in these cells resulted in increased resistance to these insults and reduced intracellular ROS formation [272]. This protection seems to be selective against environmental oxidative stress in vivo, as shown in DJͲ1 null Drosophila treated with paraquat and rotenone [273].…”

Section: Djǧ1mentioning

confidence: 80%

“…Lev et al(2008) [272] described a cellular redistribution of DJͲ1 in cells exposed to neurotoxins. This work was extended by Hayashi et al(2009) [281], who showed DJͲ1 binding to NADH dehydrogenase (ubiquinone) 1 ɲͲ subcomplex 4 (NDUFA4) and to mitochondrial encoded NADH dehydrogenase 1 (ND1), nuclear and mitochondrial DNAͲencoding subunits of complex I, respectively, validating the importance of DJͲ1 in mitochondrial function.…”

Section: Djǧ1mentioning

confidence: 99%

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Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

Perfeito

Cunha‐Oliveira

Rego

2012

Free Radical Biology and Medicine

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Section: Djǧ1mentioning

confidence: 80%

Section: Djǧ1mentioning

confidence: 99%

Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

Perfeito

Cunha‐Oliveira

Rego

2012

Free Radical Biology and Medicine

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“…DJ-1 is located both in the cytoplasm and nucleus [1] and has recently been shown to be located in mitochondria [11,[24][25][26]. It has also been reported that some parts of DJ-1 were translocated into mitochondria after cells had been subjected to oxidative stress to protect cells from oxidative stress-induced cell death [27][28][29][30]. The exact localization of DJ-1 in mitochondria, inner membrane, outer membrane or intermembrane space, is, however, still not clear, and the characteristics and function of mitochondria-resident DJ-1 are still not known.…”

Section: Introductionmentioning

confidence: 99%

DJ-1 binds to mitochondrial complex I and maintains its activity

Hayashi

Ishimori

Takahashi-Niki

et al. 2009

Biochemical and Biophysical Research Communications

170

122

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Parkinson's disease (PD) is caused by neuronal cell death, and oxidative stress and mitochondrial dysfunction are thought to be responsible for onset of PD. DJ-1, a causative gene product of a familial form of Parkinson's disease, PARK7, plays roles in transcriptional regulation and anti-oxidative stress. The possible mitochondrial function of DJ-1 has been proposed, but its exact function remains unclear. In this study, we found that DJ-1 directly bound to NDUFA4 and ND1, nuclear and mitochondrial DNA-encoding subunits of mitochondrial complex I, respectively, and was co-localized with complex I and that complex I activity was reduced in DJ-1-knockdown NIH3T3 and HEK293cells. These findings suggest that DJ-1 is an integral mitochondrial protein and that DJ-1 plays a role in maintenance of mitochondrial complex I activity.

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“…Knockdown of DJ-1 by siRNA in the SH-SY5Y human neuroblastoma cell line enhanced susceptibility to several oxidative insults, including H 2 O 2 , MPP þ , and 6-OHDA [270]. Reciprocally, DJ-1 overexpression in these cells resulted in increased resistance to these insults and reduced intracellular ROS formation [272]. This protection seems to be selective against environmental oxidative stress in vivo, as shown in DJ-1 null Drosophila treated with paraquat and rotenone [273].…”

Section: Dj-1mentioning

confidence: 79%

“…Lev et al [272] described a cellular redistribution of DJ-1 in cells exposed to neurotoxins. This work was extended by Hayashi et al [281], who showed DJ-1 binding to NADH dehydrogenase (ubiquinone) 1a-subcomplex 4 and to mitochondrial-encoded NADH dehydrogenase 1, nuclear and mitochondrial DNA-encoding subunits of complex I, respectively, validating the importance of DJ-1 in mitochondrial function.…”

Section: Dj-1mentioning

confidence: 99%

Reprint of: Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

Perfeito

Cunha‐Oliveira

Rego

2013

Free Radical Biology and Medicine

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a b s t r a c tParkinson disease (PD) is a chronic and progressive neurological disease associated with a loss of dopaminergic neurons. In most cases the disease is sporadic but genetically inherited cases also exist. One of the major pathological features of PD is the presence of aggregates that localize in neuronal cytoplasm as Lewy bodies, mainly composed of a-synuclein (a-syn) and ubiquitin. The selective degeneration of dopaminergic neurons suggests that dopamine itself may contribute to the neurodegenerative process in PD. Furthermore, mitochondrial dysfunction and oxidative stress constitute key pathogenic events of this disorder. Thus, in this review we give an actual perspective to classical pathways involving these two mechanisms of neurodegeneration, including the role of dopamine in sporadic and familial PD, as well as in the case of abuse of amphetamine-type drugs. Mutations in genes related to familial PD causing autosomal dominant or recessive forms may also have crucial effects on mitochondrial morphology, function, and oxidative stress. Environmental factors, such as MPTP and rotenone, have been reported to induce selective degeneration of the nigrostriatal pathways leading to a-syn-positive inclusions, possibly by inhibiting mitochondrial complex I of the respiratory chain and subsequently increasing oxidative stress. Recently, increased risk for PD was found in amphetamine users. Amphetamine drugs have effects similar to those of other environmental factors for PD, because long-term exposure to these drugs leads to dopamine depletion. Moreover, amphetamine neurotoxicity involves a-syn aggregation, mitochondrial dysfunction, and oxidative stress. Therefore, dopamine and related oxidative stress, as well as mitochondrial dysfunction, seem to be common links between PD and amphetamine neurotoxicity.

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Oxidative insults induce DJ-1 upregulation and redistribution: Implications for neuroprotection

Cited by 123 publications

References 26 publications

Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

DJ-1 binds to mitochondrial complex I and maintains its activity

Reprint of: Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

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