MnSOD Val-9Ala Genotype, Pro- and Anti-oxidant Environmental Modifiers, and Breast Cancer Among Women on Long Island, New York

Excessive oxidative stress may induce and promote breast carcinogenesis. Manganese superoxide dismutase (MnSOD) is critical to management of oxidative stress by catalyzing the formation of hydrogen peroxide from two superoxide anions. To examine the relationship between MnSOD Val-9Ala polymorphism, breast cancer and potential modifiers, we analyzed data from a large population-based case-control study. Study participants completed an in-home interviewer-administered questionnaire, and self-completed a Block food frequency questionnaire. Age-adjusted unconditional logistic models included 1034 cases and 1084 controls. As compared with Val/Val genotype, we found no association between MnSOD Ala/Val (OR = 0.98, 95% CI: 0.79–1.21) and Ala/Ala (OR = 1.00, 95% CI: 0.79–1.28) genotypes and breast cancer. Results did not differ by menopausal status, stage of tumor, or estrogen and progesterone receptor status. No discernable patterns of interaction were found between this MnSOD variant and anti-oxidative exposures, including fruit and vegetable intake or NSAID use, or pro-oxidant exposures, including smoking and alcohol. This study provides little evidence that variation in Val-9Ala polymorphism of MnSOD alone or through substantial interaction with key exposures believed to be pro- or anti-oxidant properties influences breast cancer risk.     

The level of manganese superoxide dismutase content is an independent prognostic factor for glioblastoma. Biological mechanisms and clinical implications

We address the issue of the role of manganese superoxide dismutase in tumorigenesis by studying a relatively homogeneous group of tumours for the correlation between amount of this anti-oxidant enzyme and prognosis. The clinical outcome of 30 patients affected by glioblastomas whose manganese superoxide dismutase content had been established at the time of first diagnosis is compared. When the survival of patients is stratified according to manganese superoxide dismutase level in the tumour, a link of these levels and prognosis can be observed. Patients with high levels of manganese superoxide dismutase show a median survival time of 6.11 months, while patients whose tumours display a low amount of MnSOD have a median survival time of 12.17 months. To assess the upstream mechanisms that sustain the increase in manganese superoxide dismutase content in brain neuroepithelial tumours, we also studied the expression of p53 in a series of 17 astrocytomas of various grading. In all tested astrocytomas, high manganese superoxide dismutase content is associated with cytoplasmic accumulation of p53. Thus glioblastomas can be divided into two distinct groups on the basis of their content of manganese superoxide dismutase, having 'better' or 'worse' prognosis, respectively. The use of this protein as a marker may help to define therapeutic strategies in the clinical management of glioblastoma.     

Manganese superoxide dismutase plays an important role in the inflammatory process and predicts disease severity and activity in patients with ulcerative colitis

The aim of this study was to investigate the expression pattern of manganese superoxide dismutase (MnSOD) in relation to inflammatory factors in ulcerative colitis (UC) and characterize this enzyme as a newly identified biomarker potentially linked to disease pathogenesis of UC. MnSOD expression was analyzed immunohistochemically in 48 formalin‐fixed and paraffin‐embedded specimens from patients with UC who had undergone endoscopical biopsy. MnSOD expression was observed in vascular endothelium, macrophages, and polymorphonuclear leukocytes within lamina propria of inflamed mucosa. The patients who did not express MnSOD tended to have stabilization of symptoms, but accompanied with status of inflammation. The MnSOD expression pattern was strongly correlated with disease type. MnSOD was expressed in polymorphonuclear leukocytes of all disease types, but cases of chronically counting and exacerbation type had particularly high frequency of immunopositive cells. MnSOD expression in macrophages was frequently observed in cases of symptom remaining type. The cases with MnSOD expression in the vascular endothelium showed a tendency to express in relapse‐remission and exacerbation of symptoms. Immunohistochemical evaluation for MnSOD expression may be useful for predicting disease severity and activity in patients with UC.     

MnSOD在非小细胞肺癌组织的表达及意义

目的研究锰超氧化物歧化酶(MnSOD)在非小细胞肺癌(NSCLC)中的表达及其与肿瘤生物学特征的关系.方法采用免疫组化法(ABC法)对50例NSCLC和15例远离肿瘤的正常肺组织中MnSOD蛋白的表达状况进行检测,分析其在NSCLC和正常肺组织中表达以及与肿瘤大小、病理分级、组织学类型、淋巴结後转移及临床分期的关系.结果MnSOD在正常肺组织表达阳性率(100%),在NSCLC组织中表达阳性率为70%,较正常肺组织明显降低(P＜0.05);MnSOD阳性表达率与肿瘤T分期有关,T3-4组MnSOD表达阳性率47.83%,明显低于T1-2组阳性表达率88.89%(P＜0.05),而与病理分级、细胞类型、临床分期临床分期及有无淋巴结转移无关.结论NSCLC肿瘤组织中MnSOD表达阳性率明显低于正常肺组织MnSOD表达阳性率,在NSCLC病人MnSOD表达阳性率T3～4组明显低于T1～2组,提示MnSOD在肺癌发生发展中可能起抑制样作用,并可用于判断NSCLC生长侵袭能力.     

Reduction of lipid and protein damage in patients with disorders of propionate metabolism under treatment: a possible protective role of l-carnitine supplementation

Disorders of propionate metabolism are autosomal recessive diseases clinically characterized by acute metabolic crises in the neonatal period and long-term neurological deficits whose pathophysiology is not completely established. There are increasing evidences demonstrating antioxidant properties for l-carnitine, which is used in the treatment of propionic and methylmalonic acidemias to increase the excretion of organic acids accumulated in tissues and biological fluids of the affected patients. In this work we aimed to evaluate lipid (malondialdehyde content) and protein (carbonyl formation and sulfhydryl oxidation) oxidative damage in plasma from patients with propionic and methylmalonic acidemias at the moment of diagnosis and during treatment with l-carnitine. We also correlated the parameters of oxidative damage with plasma total, free and esterified l-carnitine levels. We found a significant increase of malondialdehyde and carbonyl groups, as well as a reduction of sulfhydryl groups in plasma of these patients at diagnosis compared to controls. Furthermore, patients under treatment presented a marked reduction of the content of protein carbonyl groups, similar to controls, and malondialdehyde content in relation to patients at diagnosis. In addition, plasma total and free l-carnitine concentrations were negatively correlated with malondialdehyde levels. Taken together, the present data indicate that treatment significantly reduces oxidative damage in patients affected by disorders of propionate metabolism and that l-carnitine supplementation may be involved in this protection.     

Mitochondrial redox metabolism: Aging, longevity and dietary effects

Mitochondrial redox metabolism has long been considered to play important roles in mammalian aging and the development of age-related pathologies in the major oxidative organs. Both genetic and dietary manipulations of mitochondrial redox metabolism have been associated with the extension of lifespan. Here we provide a broad overview of the circumstantial evidence showing associations between mitochondrial reactive oxygen species (ROS) metabolism, aging and longevity. We address most aspects of mitochondrial ROS metabolism, from superoxide production, to ROS detoxification and the repair/removal of ROS-mediated macromolecular damage. Finally, we discuss the effects of dietary manipulations (e.g. caloric restriction, methionine restriction), dietary deficiencies (e.g. folate) and dietary supplementation (e.g. resveratrol) on mitochondrial ROS metabolism and lifespan.     

C47T polymorphism in manganese superoxide dismutase (MnSOD), antioxidant intake and survival

INTRODUCTION AND OBJECTIVE: Manganese superoxide dismutase (MnSOD), an enzyme that catalyzes superoxide radical quenching, is hypothesized to protect against premature aging. A C47T transition in the MnSOD gene may affect the enzyme's distribution to the mitochondrion, a site of high oxidative stress. We examined the association between this polymorphism and survival. METHODS: Individuals who donated a blood sample to the CLUE I and II campaigns in 1974 and 1989, respectively, and completed a food frequency questionnaire in 1989 (N=6151) were included in the analysis. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards models. Mortality follow-up extended from 1989 to 2002. RESULTS: MnSOD genotype distributions were 27% CC (wildtype homozygotes), 50% CT (heterozygotes) and 23% TT (variant homozygotes). TT and CT genotypes compared to the CC genotype were not associated with all-cause or cardiovascular disease mortality. A slight, but non-statistically significant higher risk of cancer mortality was observed for the CT (HR=1.13, 95% CI: 0.86-1.49) and TT (HR=1.24, 95% CI: 0.90-1.70) genotypes compared to CC genotype (p-trend=0.19). CONCLUSION: We did not observe an association between the C47T polymorphism in the MnSOD gene and survival. These null associations were not modified by fruit and vegetable intake, cigarette smoking status, or body mass index.