Structural Dimorphism in the Mitochondrial Targeting Sequence in the Human Manganese Superoxide Dismutase Gene: A Predictive Evidence for Conformational Change to Influence Mitochondrial Transport and a Study of Allelic Association in Parkinson's Disease

Shimoda‐Matsubayashi, Satoe; Matsumine, Hiroto; Kobayashi, Tomonori; Nakagawa‐Hattori, Yuko; Shimizu, Yumiko; Mizuno, Yoshikuni

doi:10.1006/bbrc.1996.1806

Cited by 118 publications

(171 citation statements)

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“…The authors found an amino-acid substitution (glycine to aspartic acid) in exon 9 of the catalase gene in one PD patient; the same patient also showed a decrease in red blood cell catalase activity. 145 Although similar results were obtained in another study, 146 later investigations did not find any genetic differences in the distributions of allelic frequencies of SOD2 between PD patients and controls. [147][148][149] The interpretation of these inconclusive results is problematic.…”

Section: Antioxidant Enzymessupporting

confidence: 78%

Polymorphism in candidate genes: implications for the risk and treatment of idiopathic Parkinson's disease

et al. 2004

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Idiopathic Parkinson's disease (IPD) is a progressive neurodegenerative disorder for which no restorative or neuroprotective therapy is available. Interest has recently been directed to association studies on polymorphisms of various genes, mainly those related to dopamine metabolism and transport, and their effect on response to PD, which includes primarily levodopa and dopaminomimetics. Approximately 15-20% of patients with PD do not respond to levodopa, and the majority of those who do respond develop adverse fluctuations in motor response, primarily levodopa-induced dyskinesias. This review summarizes the influence of polymorphisms in various genes on the relative risk of IPD and on levodopa efficacy. It focuses on the importance of well-designed polymorphism studies that include large samples of patients with IPD and tightly matched controls and use identical methodologies. Valid data on such polymorphisms might increase the efficacy of levodopa, decrease its side effects, and reduce the occurrence of levodopa-induced dyskinesias. They might also provide a novel diagnostic tool for PD.

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Section: Antioxidant Enzymessupporting

confidence: 78%

Polymorphism in candidate genes: implications for the risk and treatment of idiopathic Parkinson's disease

et al. 2004

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“…Polymorphisms of SOD2 have been reported to be associated with the development of neurodegenerative diseases, such as Alzheimer disease (51) and Parkinson disease (52,53), as well as psychiatric disorders, such as schizophrenia (54), depression (55), and bipolar disorder (56). Notably, neuroinflammation is closely linked to the onset and/or development of these CNS diseases (1)(2)(3)(4)(5).…”

Section: Discussionmentioning

confidence: 99%

Dual Role of Superoxide Dismutase 2 Induced in Activated Microglia

Ishihara

Takemoto

Itoh

et al. 2015

Journal of Biological Chemistry

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Background:The redox state can affect the proinflammatory responses of microglia. Results: Superoxide dismutase 2 (SOD2) knockdown in activated microglia increased the production of reactive oxygen species (ROS) as well as inflammatory cytokines. Conclusion: SOD2 negatively regulates the inflammatory cytokine expression via ROS elimination. Significance: Our findings demonstrate a novel mechanism regulating microglial proinflammatory responses via oxidative stress.

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“…The Val allele of the enzyme has lower efficiency of transport into mitochondria. 18 A recent study suggested that higher antioxidant activity due to SNP rs4880 in SOD2 may lead to poorer survival after cyclophosphamide-containing breast cancer chemotherapy, 19 and these results were partly confirmed by another study. 20 Patients with alleles related to a higher antioxidant activity experienced significantly less grade 3-4 neutropenia but had poorer progression-free survival (PFS) than women with lowactivity genotypes.…”

mentioning

confidence: 81%

Association of superoxide dismutases and NAD(P)H quinone oxidoreductases with prognosis of patients with breast carcinomas

Hubackova

Václavíková

Ehrlichová

et al. 2011

Intl Journal of Cancer

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Associations of transcript levels of oxidative stress-modifying genes SOD2, SOD3, NQO1 and NQO2 and their functional single nucleotide polymorphisms (SNPs) rs4880, rs1799895, rs2536512, rs699473, rs1800566 and rs1143684 with prognosis of breast cancer patients were studied. SNPs were assessed by allelic discrimination in a cohort of 321 breast cancer patients from the Czech Republic. Transcript levels were determined by real-time polymerase chain reaction (PCR) with absolute quantification in tumor and adjacent non-neoplastic control tissues. Both genotypes and transcript levels were then compared with available clinical data on patients. Patients carrying low activity allele Leu in NQO2 rs1143684 had a greater incidence of stage 0 or I disease (i.e., better prognosis) than patients with the Phe/Phe genotype. This association was more evident in patients without expression of progesterone receptors (p 5 0.031). Patients carrying the Thr allele in SOD3 rs2536512 SNP had a significantly greater incidence of tumors expressing estrogen receptors than patients carrying the Ala/Ala genotype (p 5 0.007). SOD3 transcript level was significantly higher in grade 1 or 2 tumors than in grade 3 tumors (p 5 0.006). Patients carrying T allele in SOD3 rs699473 SNP had significantly poorer progression-free survival (PFS) than patients carrying the CC genotype (p 5 0.038). The same applied to the subgroup of patients treated by hormonal regimens (p 5 0.021). Patients carrying the high activity Ala/Ala genotype in SOD2 (rs4880) had significantly poorer PFS than Val allele carriers in the group treated by cyclophosphamide but not hormonal regimens (p 5 0.004). Our results suggest that NQO2, SOD2 and SOD3 may significantly modify prognosis of breast cancer patients and that their significance should be further characterized.Breast cancer is the most common cancer in women. In 2008, about 1,383,523 new cases of invasive breast cancer were diagnosed worldwide. 1 The necessity of treating such a large number of patients calls for efficient tools that can be used for subgrouping patients according to estimated prognosis. A different spectrum of treatment modalities with diverse mechanisms of action and adverse effects could then be offered to various prognostic groups. Besides well-established classical prognostic factors such as tumor size, nodal status, grading and expression of hormonal receptors, numerous biological molecules are under investigation as potential prognostic biomarkers in breast carcinomas.Excess of oxidative stress, mediated by reactive oxygen species, may cause cellular deregulation leading to cell apoptosis, 2 proliferation or tumor promotion. 3 Alkylation and topoisomerase poisoning present the major mechanisms of action of cyclophosphamide and anthracyclines, respectively. Oxidative stress represents an additional cytotoxic mechanism. 4,5 One of the initial molecules of oxidative stress, superoxide anion radical, is formed by the univalent reduction of triplet-state molecular oxygen. This process is mediated by e...

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Structural Dimorphism in the Mitochondrial Targeting Sequence in the Human Manganese Superoxide Dismutase Gene: A Predictive Evidence for Conformational Change to Influence Mitochondrial Transport and a Study of Allelic Association in Parkinson's Disease

Cited by 118 publications

References 0 publications

Polymorphism in candidate genes: implications for the risk and treatment of idiopathic Parkinson's disease

Polymorphism in candidate genes: implications for the risk and treatment of idiopathic Parkinson's disease

Dual Role of Superoxide Dismutase 2 Induced in Activated Microglia

Association of superoxide dismutases and NAD(P)H quinone oxidoreductases with prognosis of patients with breast carcinomas

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