Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The wide media coverage given recently to a study correlating higher selenium levels with a reduced risk of advanced prostate cancer is but the latest addition to a growing body of epidemiological findings which link dietary selenium deficiency to diseases as diverse as cancer, heart disease, arthritis and AIDS. Indeed, selenium has a long history of association with human health and disease. Moreover, direct evidence is now emerging for specific beneficial effects of dietary selenium supplementation. Thus, the pharmacology, biology and biochemistry of selenium metabolism have become subjects of intense current interest. At the molecular level, selenium (as selenocysteine) is an essential component of the active sites of the enzymes glutathione peroxidase, iodothyronine 5'-deiodinase and mammalian thioredoxin reductase, and is also present in several other mammalian selenoproteins. Both glutathione peroxidase and thioredoxin reductase catalyse reactions essential to the protection of cellular components against oxidative and free radical damage. As a consequence of the growing recognition of the important biological role of selenium, a number of novel pharmaceutical agents, either selenium-based or which target specific aspects of selenium metabolism, are under development. Among these are orally active selenium-based antihypertensive agents, anticancer, antiviral, immunosuppressive and antimicrobial agents, and organoselenium compounds which reduce oxidative tissue damage and oedema. It can be anticipated that as our understanding of the basic biology and biochemistry of selenium increases, future efforts will uncover even more sophisticated approaches for the rational development of new selenium-based pharmaceutical agents.
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PMID:Selenium-based drug design: rationale and therapeutic potential. 1599 3

Oxidative stress significantly contributes to heart disease, and thus might be a promising target for ameliorating heart failure. Mounting evidence suggests that selenium has chemotherapeutic potential for treating heart disease due to its regulation of selenoproteins, which play antioxidant regulatory roles. Oxidative stress-induced cardiomyocyte cell cycle arrest contributes to the loss of cardiomyocytes during heart failure. The protective effects and mechanism of selenium against oxidative stress-induced cell cycle arrest in cardiomyocytes warrant further study. H9c2 rat cardiomyoblast cells were treated with hydrogen peroxide in the presence or absence of selenium supplementation. Na2SeO3 pretreatment alleviated H2O2-induced oxidative stress, increased thioredoxin reductase (TXNRD) activity and glutathione peroxidase (GPx) activity and counteracted the H2O2-induced cell cycle arrest at the S phase. These effects were accompanied by attenuation of the H2O2-induced strengthening of the G2/M-phase inhibitory system, including increased mRNA and protein levels of cyclin-dependent kinase 1 (CDK1) and decreased p21 mRNA levels. Notably, Na2SeO3 pretreatment activated the PI3K/AKT signaling pathway, and inhibition of PI3K counteracted the protective effects of selenium on H2O2-induced cell cycle arrest. We corroborated our findings in vivo by inducing oxidative stress in pig heart by feeding a selenium deficient diet, which decreased the TXNRD activity, inactivated PI3K/AKT signaling and strengthened the G2/M-phase inhibitory system. We concluded that the cardioprotective effects of selenium supplementation against oxidative stress-induced cell cycle arrest in cardiomyocytes might be mediated by the selenoprotein-associated (GPx and TXNRD) antioxidant capacity, thereby activating redox status-associated PI3K/AKT pathways, which promote cell cycle progression by targeting the G2/M phase inhibitory system. This study provides new insight into the underlying mechanisms of cardioprotection effects of selenium at the cellular level.
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PMID:Selenium supplementation protects against oxidative stress-induced cardiomyocyte cell cycle arrest through activation of PI3K/AKT. 3323 45