Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative stress may enhance prostatic carcinogenesis. A polymorphism [valine (V) --> alanine (A)] of manganese superoxide dismutase (MnSOD), the primary antioxidant enzyme in mitochondria, has been recently associated with prostate cancer. We examined the relationship between prostate cancer and the MnSOD polymorphism and its interactions with baseline plasma antioxidant levels (selenium, lycopene, and alpha-tocopherol) and beta-carotene treatment among 567 cases and 764 controls nested in the prospective Physicians' Health Study. We found little overall association between MnSOD polymorphism and prostate cancer risk; however, this polymorphism significantly modified risk of prostate cancer associated with prediagnostic plasma antioxidants (P(interaction) > or = 0.05). Among men with the AA genotype, high selenium level (4th versus 1st quartile) was associated with a relative risk (RR) of 0.3 [95% confidence interval (CI), 0.2-0.7] for total prostate cancer; for clinically aggressive prostate cancer, the RR was 0.2 (95% CI, 0.1-0.5). In contrast, among men with the VV/VA genotype, the RRs were 0.6 (0.4-1.0) and 0.7 (0.4-1.2) for total and clinically aggressive prostate cancer. These patterns were similar for lycopene and alpha-tocopherol and were particularly strong when these antioxidants and selenium were combined; men with the AA genotype had a 10-fold gradient in risk for aggressive prostate cancer across quartiles of antioxidant status. Men with AA genotype who were randomly assigned to beta-carotene treatment (versus placebo) had a RR of 0.6 (95% CI, 0.2-0.9; P(interaction) = 0.03) for fatal prostate cancer, but no significant association was observed in men with the VV/VA genotype. Both endogenous and exogenous antioxidants play an important and interdependent role in preventing clinically significant prostate cancer.
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PMID:Manganese superoxide dismutase polymorphism, prediagnostic antioxidant status, and risk of clinical significant prostate cancer. 1578 67

Oxidative stress has been implicated in the pathogenesis of male infertility. Paraoxonase-1 (PON-1) is a high-density lipoprotein-associated antioxidant enzyme that prevents oxidative modification of low-density lipoprotein. Our aims in the study were to investigate 1) seminal PON-1 activity in subfertile men and 2) whether seminal PON-1 activity had any relationship to semen parameters. The study included 28 men with idiopathic subfertility, 32 subfertile men with abnormal semen parameters, and 30 fertile male volunteers. Seminal PON-1 activity was measured spectrophotometrically. Seminal total antioxidant status (TAS) and total oxidant status (TOS) were determined by using colorimetric methods. Oxidative stress index (OSI) was calculated as ([TOS/TAS] x 100). TOS and OSI were significantly higher and PON-1 activity and TAS were significantly lower in subfertile men with abnormal semen parameters than in men with idiopathic subfertility and fertile donors. PON-1 activity was also strongly correlated with sperm concentration (r = .68, P < .0001), motility (r = .58, P < .0001), and morphology (r = .62, P < .0001) in the overall group. The receiver operating characteristic curve analysis revealed a high diagnostic value for PON-1 activity with respect to male-factor subfertility, with an area under curve of .95 (95% confidence interval = 0.89-1.01), sensitivity = 97%, and specificity = 88%. Men with abnormal semen parameters have decreased levels of PON-1 activity in their seminal plasma. This may play an important role in the pathogenesis of male-factor subfertility.
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PMID:Paraoxonase-1 activity in subfertile men and relationship to sperm parameters. 1893 Sep 7

Oxidative stress generated by ascorbate-driven menadione redox cycling kills MCF7 cells by a concerted mechanism including glycolysis inhibition, loss of calcium homeostasis, DNA damage and changes in mitogen activated protein kinases (MAPK) activities. Cell death is mediated by necrosis rather than apoptosis or macroautophagy. Neither 3-methyladenine nor Z-VAD affects cytotoxicity by ascorbate/menadione (Asc/Men). BAPTA-AM, by restoring cellular capacity to reduce MTT, underlines the role of calcium in the necrotic process. Oxidative stress-mediated cell death is shown by the opposite effects of N-acetylcysteine and 3-aminotriazole. Moreover, oxidative stress induces DNA damage (protein poly-ADP-ribosylation and gamma-H2AX phosphorylation) and inhibits glycolysis. Asc/Men deactivates extracellular signal-regulated kinase (ERK) while activating p38, suggesting an additional mechanism to kill MCF7 cells. Since ascorbate is taken up by cancer cells and, due to their antioxidant enzyme deficiency, oxidative stress should affect cancer cells to a greater extent than normal cells. This differential sensitivity may have clinical applications.
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PMID:Menadione reduction by pharmacological doses of ascorbate induces an oxidative stress that kills breast cancer cells. 1948 29