Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peroxiredoxin II, a cytosolic isoform of the antioxidant enzyme family, has been implicated in cancer-associated cell death and apoptosis, but its functional role in the heart remains to be elucidated. Interestingly, the expression levels of peroxiredoxin II were decreased in mouse hearts upon ischemia-reperfusion, while they were elevated in two genetically modified hyperdynamic hearts with phospholamban ablation or protein phosphatase 1 inhibitor 1 overexpression. To delineate the functional significance of altered peroxiredoxin II expression, adenoviruses encoding sense or antisense peroxiredoxin II were generated; cardiomyocytes were infected, and then subjected to H(2)O(2) treatment to mimic oxidative stress-induced cell death and apoptosis. H(2)O(2) stimulation resulted in a significant decrease of endogenous peroxiredoxin II expression, along with reduced cell viability in control cells. However, overexpression of peroxiredoxin II significantly protected from H(2)O(2)-induced apoptosis and necrosis, while downregulation of this enzyme promoted the detrimental effects of oxidative stress in cardiomyocytes. The beneficial effects of peroxiredoxin II were associated with increased Bcl-2 expression, decreased expression of Bax and attenuated activity of caspases 3, 9 and 12. Furthermore, there were no significant alterations in the expression levels of the other five isoforms of peroxiredoxin, as well as active catalase or glutathione peroxidase-1 after ischemia-reperfusion or H(2)O(2) treatment. These findings suggest that peroxiredoxin II may be a unique antioxidant in the cardiac system and may represent a potential target for cardiac protection from oxidative stress-induced injury.
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PMID:Protection of peroxiredoxin II on oxidative stress-induced cardiomyocyte death and apoptosis. 1903 Sep 11

Peroxiredoxins (Prxs) are antioxidant enzymes that protect cells from oxidative stress by reducing intracellular accumulation of reactive oxygen species (ROS). In mammalian cells, the six Prx isoforms are ubiquitously expressed in diverse intracellular locations. They are involved in the regulation of various physiological processes including cell growth, differentiation, apoptosis, immune response and metabolism as well as intracellular ROS homeostasis. Although there are increasing evidences that Prxs are involved in carcinogenesis of many cancers, their role in cancer is controversial. The ROS levels in cancer cells are increased compared to normal cells, thus promoting cancer development. Nevertheless, for various cancer types, an overexpression of Prxs has been found to be associated with poor patient prognosis, and an increasing number of studies have reported that tumorigenesis is either facilitated or inhibited by regulation of cancer-associated signaling pathways. This review summarizes Prx isoforms and their basic functions, the relationship between the expression level and the physiological role of Prxs in cancer cells, and their roles in regulating cancer-associated signaling pathways.
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PMID:The Role of Peroxiredoxin Family in Cancer Signaling. 3136 Jun 86

Cysteine thiols of many cancer-associated proteins are attractive targets of anticancer agents. Herein, we unequivocally demonstrate a distinct thiol-targeting property of gold(III) mesoporphyrin IX dimethyl ester (AuMesoIX) and its anticancer activities. While the binding of cysteine thiols with metal complexes usually occurs via M-S bond formation, AuMesoIX is unique in that the meso-carbon atom of the porphyrin ring is activated by the gold(III) ion to undergo nucleophilic aromatic substitution with thiols. AuMesoIX was shown to modify reactive cysteine residues and inhibit the activities of anticancer protein targets including thioredoxin, peroxiredoxin, and deubiquitinases. Treatment of cancer cells with AuMesoIX resulted in the formation of gold-bound sulfur-rich protein aggregates, oxidative stress-mediated cytotoxicity, and accumulation of ubiquitinated proteins. Importantly, AuMesoIX exhibited effective antitumor activity in mice. Our study has uncovered a gold(III)-induced ligand scaffold reactivity for thiol targeting that can be exploited for anticancer applications.
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PMID:An anticancer gold(III)-activated porphyrin scaffold that covalently modifies protein cysteine thiols. 3189 86