Mitochondrial peroxiredoxin‐3 protects hippocampal neurons from excitotoxic injury <i>in vivo</i>

Hattori, Fumiyuki; Murayama, Norihito; Noshita, Takafumi; Oikawa, Shinzo

doi:10.1046/j.1471-4159.2003.01918.x

Cited by 131 publications

(92 citation statements)

References 35 publications

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“…Proteome analysis reveals up-regulation of PRX1 and PRX6 in experimental models of familial amyotrophic lateral sclerosis (66,67). Using both in vivo and in vitro models of excitotoxic injury, two independent studies indicate that overexpression of PRX3 or PRX5 provides a certain degree of neuroprotection in these models (68,69), thereby providing evidence for the involvement of certain isoforms of PRX in the progression of neurodegenerative disorders. However, none of these studies showed generation of the oxidized forms of PRX.…”

Section: Discussionmentioning

confidence: 99%

Oxidative Modification of Peroxiredoxin Is Associated with Drug-induced Apoptotic Signaling in Experimental Models of Parkinson Disease

Lee

Park

Shin

et al. 2008

Journal of Biological Chemistry

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The aim of this study was to investigate changes in protein profiles during the early phase of dopaminergic neuronal death using two-dimensional gel electrophoresis in conjunction with mass spectrometry. Several protein spots were identified whose expression was significantly altered following treatment of MN9D dopaminergic neuronal cells with 6-hydroxydopamine (6-OHDA). In particular, we detected oxidative modification of thioredoxin-dependent peroxidases (peroxiredoxins; PRX) in treated MN9D cells. Oxidative modification of PRX induced by 6-OHDA was blocked in the presence of N-acetylcysteine, suggesting that reactive oxygen species (ROS) generated by 6-OHDA induce oxidation of PRX. These findings were confirmed in primary cultures of mesencephalic neurons and in rat brain injected stereotaxically. Overexpression of PRX1 in MN9D cells (MN9D/PRX1) exerted neuroprotective effects against death induced by 6-OHDA through scavenging of ROS. Consequently, generation of both superoxide anion and hydrogen peroxide following 6-OHDA treatment was decreased in MN9D/PRX1. Furthermore, overexpression of PRX1 protected cells against 6-OHDA-induced activation of p38 MAPK and subsequent activation of caspase-3. In contrast, 6-OHDA-induced apoptotic death signals were enhanced by RNA interference-targeted reduction of PRX1 in MN9D cells. Taken together, our data suggest that the redox state of PRX may be intimately involved in 6-OHDA-induced dopaminergic neuronal cell death and also provide a molecular mechanism by which PRX1 exerts a protective role in experimental models of Parkinson disease. Parkinson disease (PD)3 is a common neurodegenerative disorder characterized by progressive degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (1). Clinical manifestations, such as resting tremor, slowness of movement, stiffness, and postural instability in patients with PD are consequences of the loss of DA neurons and the resulting depletion of dopamine in the striatum. Most PD cases are sporadic, and its etiology is incompletely understood; however, an increasing body of evidence suggests that oxidative stress, mitochondrial dysfunction, and impairment of the ubiquitinproteasome system may be involved in the pathogenesis of PD (2-5). Recent studies indicate that mutations in several genes appear to cause a familial form of PD (6), and mutations in these genes seem to share common pathways underlying the pathogenesis of a sporadic form of PD.DA neurons are vulnerable to neurodegeneration because of their high levels of reactive oxygen species (ROS) (7); enzymatic metabolism of dopamine produces hydrogen peroxide and superoxide radicals, and intracellular autoxidation of dopamine induces the formation of dopamine-quinone, leading to the generation of hydroxyl radical when combined with iron (7, 8). Furthermore, there is a significant alteration in levels or activities of antioxidant enzymes in the substantia nigra (9 -13). Among many potential consequences of oxidative stress, surges in ROS render DA neuron...

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Section: Discussionmentioning

confidence: 99%

Oxidative Modification of Peroxiredoxin Is Associated with Drug-induced Apoptotic Signaling in Experimental Models of Parkinson Disease

Lee

Park

Shin

et al. 2008

Journal of Biological Chemistry

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“…A down-regulation of Prx-3 has been described in various experimental models that are characterized by an increased cellular oxidative stress [153][154][155]. In human heart failure Brixius et al [156] have also reported a selective down-regulation of the mitochondrial Prx-3 and Prx-5 as well as that of the extracellular Prx-4 isoform and that of the cytosolic Prx-6, while the cytosolic Prx-1 and Prx-2 isoforms are unaffected by the enhanced ROS production.…”

Section: Down-regulation Of Peroxiredoxin-3 Expression By Angiotensinmentioning

confidence: 99%

Modulation of Reactive Oxygen Species and Collagen Synthesis by Angiotensin II in Cardiac Fibroblasts

Lijnen¹

2011

TOHYPERJ

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Angiotensin II increases the NAD(P)H-dependent superoxide anion production and the intracellular generation of reactive oxygen species in cardiac fibroblasts and apocynin, a NAD(P)H oxidase inhibitor, abrogates this rise. The membrane associated NAD(P)H oxidase complex is the predominant source of superoxide anion and reactive oxygen species generation in angiotensin II-stimulated adult cardiac fibroblasts. Inhibition of this NAD(P)H oxidase complex with apocynin completely blocks the angiotensin II-stimulated collagen production, collagen I and III protein and mRNA expression.Superoxide anion production is also increased by the Cu,Zn-superoxide dismutase (SOD) inhibitor diethyldithiocarbamic acid (DETC) and decreased by the superoxide scavenger tempol in control and ANG II-treated fibroblasts. ANG II and DETC stimulate the collagen production and the collagen I and fibronectin content in fibroblasts. The SOD mimetics tempol and EUK-8 as well as polyethyleneglycol-SOD reduce the collagen production.ANG II also decreases the activity and mRNA and protein expression of the mitochondrial antioxidants Mn-SOD and peroxiredoxin-3. Upon phosphorylation of Akt by ANG II, P-Akt is translocated from the cytoplasm to the nucleus and nuclear phosphorylation of FOXO3a by P-Akt leads to relocalisation of FOXO3a from the nucleus to the cytosol, resulting in a decrease in its transcriptional activity and in Mn-SOD expression. These data indicate that ANG II inactivates FOXO3a by activating Akt and this leads to a reduction in the expression of the antioxidant Mn-SOD. A role of SOD and the formed reactive oxygen species in the regulation and organization of collagen in cardiac fibroblasts is suggested.

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“…7 Furthermore, in vivo transfer of the Prx-3 gene protected neurons against cell death induced by oxidative stress. 8 These beneficial characteristics make Prx-3 an important candidate for therapy against LV failure after MI, in which ROS production has been demonstrated to be increased within the mitochondria. 1,4 Although several previous reports showed the beneficial effects of antioxidants on heart failure, 9,10 no study has ever been performed to specifically examine the protective role of Prx-3.…”

Section: Clinical Perspective P 1786mentioning

confidence: 99%

Overexpression of Mitochondrial Peroxiredoxin-3 Prevents Left Ventricular Remodeling and Failure After Myocardial Infarction in Mice

Ide²,

et al. 2006

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Background-Mitochondrial oxidative stress and damage play major roles in the development and progression of left ventricular (LV) remodeling and failure after myocardial infarction (MI). We hypothesized that overexpression of the mitochondrial antioxidant, peroxiredoxin-3 (Prx-3), could attenuate this deleterious process. Methods and Results-We created MI in 12-to 16-week-old, male Prx-3-transgenic mice (TGϩMI, nϭ37) and nontransgenic wild-type mice (WTϩMI, nϭ39) by ligating the left coronary artery. Prx-3 protein levels were 1.8 times higher in the hearts from TG than WT mice, with no significant changes in other antioxidant enzymes. At 4 weeks after MI, LV thiobarbituric acid-reactive substances in the mitochondria were significantly lower in TGϩMI than in WTϩMI mice (meanϮSEM, 1.5Ϯ0.2 vs 2.2Ϯ0.2 nmol/mg protein; nϭ8 each, PϽ0.05). LV cavity dilatation and dysfunction were attenuated in TGϩMI compared with WTϩMI mice, with no significant differences in infarct size (56Ϯ1% vs 55Ϯ1%; nϭ6 each, PϭNS) and aortic pressure between groups. Mean LV end-diastolic pressures and lung weights in TGϩMI mice were also larger than those in WTϩsham-operated mice but smaller than those in WTϩMI mice. Improvement in LV function in TGϩMI mice was accompanied by a decrease in myocyte hypertrophy, interstitial fibrosis, and apoptosis in the noninfarcted LV. Mitochondrial DNA copy number and complex enzyme activities were significantly decreased in WTϩMI mice, and this decrease was also ameliorated in TGϩMI mice. Conclusions-Overexpression of Prx-3 inhibited LV remodeling and failure after MI. Therapies designed to interfere with mitochondrial oxidative stress including the antioxidant Prx-3 might be beneficial in preventing cardiac failure.

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Mitochondrial peroxiredoxin‐3 protects hippocampal neurons from excitotoxic injury in vivo

Cited by 131 publications

References 35 publications

Oxidative Modification of Peroxiredoxin Is Associated with Drug-induced Apoptotic Signaling in Experimental Models of Parkinson Disease

Oxidative Modification of Peroxiredoxin Is Associated with Drug-induced Apoptotic Signaling in Experimental Models of Parkinson Disease

Modulation of Reactive Oxygen Species and Collagen Synthesis by Angiotensin II in Cardiac Fibroblasts

Overexpression of Mitochondrial Peroxiredoxin-3 Prevents Left Ventricular Remodeling and Failure After Myocardial Infarction in Mice

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