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)

Thioredoxin reductase (TR) activity on primary melanomas and in surrounding skin is regulated by calcium and, therefore, TR activity can be used to measure the flux of calcium between primary tumors and their surrounding epidermis. Calcium uptake in human melanotic melanoma cell lines SKmel-23 (metastatic) and BC-PT-1 (primary) is related to the density of beta-2-adrenoceptors. The non-pigmented cell line HT-144 (metastatic), did not express beta-2-adrenoceptors, yielding a slow rate of calcium uptake compared to SKmel-23 and BC-PT-1. Cell extracts from melanotic and amelanotic melanoma tissues did not contain a phenylethanolamine-N-methyltransferase (PNMT) for the biosynthesis of epinephrine from norepinephrine and S-adenosylmethionine. However, human full-thickness skin, epidermis and cell cultures of human keratinocytes contained significant PNMT activities. Taken together, these results indicate that (a), TR can be used to monitor calcium flux between primary melanomas and their surrounding skin and vice versa and (b), calcium uptake may be regulated by stimulation of beta-2-adrenoceptors on melanotic melanomas by epinephrine synthesized in the surrounding skin.
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PMID:Calcium transport and regulation in human primary and metastatic melanoma. 132 82

Thioredoxin reductase has been purified from human metastatic melanotic melanoma and amelanotic melanoma tissues. Enzyme from the melanotic melanoma tissue contains bound calcium showing classical sigmoidal allosteric kinetics, whereas enzyme from the amelanotic melanoma yielded normal Michaelis-Menten saturation with substrate. Calcium inhibition can be partially reversed by oxidized thioredoxin. 45Ca has been used to label the amelanotic melanoma enzyme in order to determine the number of calcium-binding sites. These isotope experiments yielded only one calcium-binding site per enzyme molecule. Enzyme labeled with 45Ca was dialyzed for 24 h without loss of radioactivity, but the addition of oxidized thioredoxin to this labeled enzyme caused 60% calcium exchange in 24 h. Comparative studies with Escherichia coli thioredoxin reductase showed similar calcium inhibition as well as partial reactivation with oxidized thioredoxin. The enzyme from E. coli previously sequenced by others, showed considerable homology with the first EF-hands calcium-binding site of calmodulin. Detailed calcium-binding studies indicated that 10(-5) M of this fast exchange ion was sufficient to cause allosteric regulation in 10 min. This strong calcium-binding property could explain the allosteric nature of the thioredoxin reductase purified from human metastatic melanotic melanoma and its role in the regulation of melanin biosynthesis.
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PMID:Calcium regulates thioredoxin reductase in human metastatic melanoma. 276 62