Matches in SemOpenAlex for { <https://semopenalex.org/work/W1988046281> ?p ?o ?g. }
- W1988046281 endingPage "78" @default.
- W1988046281 startingPage "72" @default.
- W1988046281 abstract "Dithiocarbamates and organotins can inhibit enzymes by interacting with functionally essential sulfhydryl groups. Both classes of chemicals were shown to inhibit human 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), which converts active cortisol into inactive cortisone and has a role in renal and intestinal electrolyte regulation and in the feto-placental barrier to maternal glucocorticoids. In fish, 11β-HSD2 has a dual role by inactivating glucocorticoids and generating the major androgen 11-ketotestosterone. Inhibition of this enzyme may enhance glucocorticoid and diminish androgen effects in fish. Here, we characterized 11β-HSD2 activity of the model species zebrafish. A comparison with human and mouse 11β-HSD2 revealed species-specific substrate preference. Unexpectedly, assessment of the effects of thiram and several organotins on the activity of zebrafish 11β-HSD2 showed weak inhibition by thiram and no inhibition by any of the organotins tested. Sequence comparison revealed the presence of an alanine at position 253 on zebrafish 11β-HSD2, corresponding to cysteine-264 in the substrate-binding pocket of the human enzyme. Substitution of alanine-253 by cysteine resulted in a more than 10-fold increased sensitivity of zebrafish 11β-HSD2 to thiram. Mutating cysteine-264 on human 11β-HSD2 to serine resulted in 100-fold lower inhibitory activity. Our results demonstrate significant species differences in the sensitivity of human and zebrafish 11β-HSD2 to inhibition by thiram and organotins. Site-directed mutagenesis revealed a key role of cysteine-264 in the substrate-binding pocket of human 11β-HSD2 for sensitivity to sulfhydryl modifying agents." @default.
- W1988046281 created "2016-06-24" @default.
- W1988046281 creator A5046296909 @default.
- W1988046281 creator A5049947406 @default.
- W1988046281 creator A5079083426 @default.
- W1988046281 creator A5083927330 @default.
- W1988046281 creator A5089405597 @default.
- W1988046281 date "2012-11-01" @default.
- W1988046281 modified "2023-10-16" @default.
- W1988046281 title "Species-specific differences in the inhibition of human and zebrafish 11β-hydroxysteroid dehydrogenase 2 by thiram and organotins" @default.
- W1988046281 cites W1582124500 @default.
- W1988046281 cites W1964459472 @default.
- W1988046281 cites W1965210701 @default.
- W1988046281 cites W1971864105 @default.
- W1988046281 cites W1974004231 @default.
- W1988046281 cites W1974488448 @default.
- W1988046281 cites W1980494908 @default.
- W1988046281 cites W1982425917 @default.
- W1988046281 cites W1985040718 @default.
- W1988046281 cites W1992472104 @default.
- W1988046281 cites W1993237941 @default.
- W1988046281 cites W1999156812 @default.
- W1988046281 cites W2005195078 @default.
- W1988046281 cites W2005595350 @default.
- W1988046281 cites W2013710072 @default.
- W1988046281 cites W2015078443 @default.
- W1988046281 cites W2019314939 @default.
- W1988046281 cites W2019860323 @default.
- W1988046281 cites W2026200312 @default.
- W1988046281 cites W2039227803 @default.
- W1988046281 cites W2040063071 @default.
- W1988046281 cites W2041114367 @default.
- W1988046281 cites W2044697629 @default.
- W1988046281 cites W2044800918 @default.
- W1988046281 cites W2046399147 @default.
- W1988046281 cites W2046405586 @default.
- W1988046281 cites W2059822034 @default.
- W1988046281 cites W2064795124 @default.
- W1988046281 cites W2065609759 @default.
- W1988046281 cites W2067223573 @default.
- W1988046281 cites W2071878822 @default.
- W1988046281 cites W2075286891 @default.
- W1988046281 cites W2076822580 @default.
- W1988046281 cites W2083555686 @default.
- W1988046281 cites W2087141513 @default.
- W1988046281 cites W2090133969 @default.
- W1988046281 cites W2092106504 @default.
- W1988046281 cites W2092950628 @default.
- W1988046281 cites W2094339603 @default.
- W1988046281 cites W2097600921 @default.
- W1988046281 cites W2098299168 @default.
- W1988046281 cites W2113560501 @default.
- W1988046281 cites W2120543890 @default.
- W1988046281 cites W2125535253 @default.
- W1988046281 cites W2132557395 @default.
- W1988046281 cites W2136138120 @default.
- W1988046281 cites W2139883678 @default.
- W1988046281 cites W2144950148 @default.
- W1988046281 cites W2151574084 @default.
- W1988046281 cites W2160137706 @default.
- W1988046281 cites W2160710609 @default.
- W1988046281 cites W2163557466 @default.
- W1988046281 cites W2164872379 @default.
- W1988046281 cites W2165037530 @default.
- W1988046281 cites W34091767 @default.
- W1988046281 cites W4242814566 @default.
- W1988046281 cites W4243048085 @default.
- W1988046281 doi "https://doi.org/10.1016/j.tox.2012.07.001" @default.
- W1988046281 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22796344" @default.
- W1988046281 hasPublicationYear "2012" @default.
- W1988046281 type Work @default.
- W1988046281 sameAs 1988046281 @default.
- W1988046281 citedByCount "21" @default.
- W1988046281 countsByYear W19880462812013 @default.
- W1988046281 countsByYear W19880462812014 @default.
- W1988046281 countsByYear W19880462812015 @default.
- W1988046281 countsByYear W19880462812017 @default.
- W1988046281 countsByYear W19880462812018 @default.
- W1988046281 countsByYear W19880462812019 @default.
- W1988046281 countsByYear W19880462812020 @default.
- W1988046281 countsByYear W19880462812021 @default.
- W1988046281 countsByYear W19880462812022 @default.
- W1988046281 countsByYear W19880462812023 @default.
- W1988046281 crossrefType "journal-article" @default.
- W1988046281 hasAuthorship W1988046281A5046296909 @default.
- W1988046281 hasAuthorship W1988046281A5049947406 @default.
- W1988046281 hasAuthorship W1988046281A5079083426 @default.
- W1988046281 hasAuthorship W1988046281A5083927330 @default.
- W1988046281 hasAuthorship W1988046281A5089405597 @default.
- W1988046281 hasConcept C104317684 @default.
- W1988046281 hasConcept C161176658 @default.
- W1988046281 hasConcept C181199279 @default.
- W1988046281 hasConcept C185592680 @default.
- W1988046281 hasConcept C2776414213 @default.
- W1988046281 hasConcept C2776878037 @default.
- W1988046281 hasConcept C2777855856 @default.
- W1988046281 hasConcept C2779201268 @default.
- W1988046281 hasConcept C55493867 @default.