Biotransformations of antidiabetic vanadium prodrugs in mammalian cells and cell culture media [electronic resource] : A XANES spectroscopic study

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Tác giả:

Ngôn ngữ: eng

Ký hiệu phân loại: 540 Chemistry and allied sciences

Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2015

Mô tả vật lý: Size: p. 6707-6718 : , digital, PDF file.

Bộ sưu tập: Metadata

ID: 261181

 The antidiabetic activities of vanadium(V) and -(IV) prodrugs are determined by their ability to release active species upon interactions with components of biological media. The first X-ray absorption spectroscopic study of the reactivity of typical vanadium (V) antidiabetics, vanadate ([V<
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 O<
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 3?<
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 , A) and a vanadium(IV) bis(maltolato) complex (B), with mammalian cell cultures has been performed using HepG2 (human hepatoma), A549 (human lung carcinoma), and 3T3-L1 (mouse adipocytes and preadipocytes) cell lines, as well as the corresponding cell culture media. X-ray absorption near-edge structure data were analyzed using empirical correlations with a library of model vanadium(V), -(IV), and -(III) complexes. Both A and B ([V] = 1.0 mM) gradually converged into similar mixtures of predominantly five- and six-coordinate VV species (~75% total V) in a cell culture medium within 24 h at 310 K. Speciation of V in intact HepG2 cells also changed with the incubation time (from ~20% to ~70% V<
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 IV<
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  of total V), but it was largely independent of the prodrug used (A or B) or of the predominant V oxidation state in the medium. Subcellular fractionation of A549 cells suggested that V<
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  reduction to V<
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 IV<
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  occurred predominantly in the cytoplasm, while accumulation of V<
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  in the nucleus was likely to have been facilitated by noncovalent bonding to histone proteins. The nuclear V<
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 V<
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  is likely to modulate the transcription process and to be ultimately related to cell death at high concentrations of V, which may be important in anticancer activities. Mature 3T3-L1 adipocytes (unlike for preadipocytes) showed a higher propensity to form V<
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 IV<
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  species, despite the prevalence of V<
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 V<
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  in the medium. Lastly, the distinct V biochemistry in these cells is consistent with their crucial role in insulin-dependent glucose and fat metabolism and may also point to an endogenous role of V in adipocytes.
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