Extraskeletal Effects of Vitamin D by Emilia Pauline Liao

Author:Emilia Pauline Liao
Language: eng
Format: epub, pdf
Publisher: Springer International Publishing, Cham

Differentiation EC50 M e−11 (EMR)

Calcaemic action Ca2+ (serum) mg/dL

VDR-binding IC50 M e−10 (RBA)

1,25D3

 53.47 (1)

107.0 ± 4.5

23.20 (100)

PRI-1907

  5.952 (0.11)

 74.8 ± 2.2

61.72 (37)

PRI-5100

112.8 (2.12)

 85.5 ± 3.7

 5.599 (414)

PRI-5101

117.9 (2.22)

 90.3 ± 3.2

 4.921 (471)

PRI-5201

  3.397 (0.063)

 93.3 ± 2.3

11.193 (194)

PRI-5202

  1.788 (0.033)

 80.5 ± 1.9

35.98 (64)

Interestingly, the anticancer capacities of the low-calcaemic analogues of 1,25D2 do not correlate with the affinities of the analogues to VDR (Table 6.1). All of the actions of 1,25D on leukaemia cells cannot be attributed to VDR-driven transcription. As considered above, 1,25D induces rapid events within cells, and there might be alternative receptors. The rapid action of 1,25D on intestinal cells has been attributed to binding to Pdia3. Furthermore, megalin and cubilin transport vitamin D metabolites, coupled to serum vitamin D-binding protein (DBP), through the cell membrane. Receptor endocytosis, and recycling, can rapidly generate intracellular signals through the Rab5/PI3-kinase pathway. In essence, interplay between genomic and non-genomic events, different signal transduction pathways and the ability of a given analogue to stabilise VDR in the cell nucleus are all important to the biological activity of analogues. A resolve as to the extent analogues of 1,25D2 and 1,25D3 can elicit particular events within cells is important to the development of the very best, particularly non-calcaemic analogue, for use in antileukaemia therapy.

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