Biological activities of 2alpha-substituted analogues of 1alpha,25-dihydroxyvitamin D3 in transcriptional regulation and human promyelocytic leukemia (HL-60) cell proliferation and differentiation.
Biological activities of 2alpha-substituted 1alpha,25-dihydroxyvitamin D3 analogues were evaluated in vitro. Their binding affinity was examined with calf thymus cytosolic vitamin D receptor (VDR) and rat plasma vitamin D-binding protein (DBP). In addition, the transcriptional activity of the analogues was measured using a rat 25-hydroxyvitamin D3-24-hydroxylase gene promoter, a human osteocalcin gene promoter, and VDR-GAL4 system. This study investigated the biological activities of 2alpha-substituted analogues in comparison with 2beta-substitued analogues at the molecular level, with regard to the structural differences of alkyl, hydroxyalkyl, hydroxyalkoxy substituents at the 2-position of 1alpha,25-dihydroxyvitamin D3.
Takahashi
Eiji
E
Department of Hygienic Sciences, Kobe Pharmaceutical University, Japan.
Nakagawa
Kimie
K
Suhara
Yoshitomo
Y
Kittaka
Atsushi
A
Nihei
Ken-ichi
K
Konno
Katsuhiro
K
Takayama
Hiroaki
H
Ozono
Keiichi
K
Okano
Toshio
T
D000818:Animals; D039481:CD11b Antigen / Q000096:biosynthesis; D002117:Calcitriol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D015394:Molecular Structure; D015675:Osteocalcin / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation / Q000187:drug effects* / Q000235:genetics; D014162:Transfection; D014809:Vitamin D-Binding Protein / Q000235:genetics / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
D039481:CD11b Antigen; D018950:Lipopolysaccharide Receptors; D018167:Receptors, Calcitriol; D014809:Vitamin D-Binding Protein; D015675:Osteocalcin; D008156:Luciferases; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol