1,25-dihydroxyvitamin D3 enhances the transcription and expression of the inositol trisphosphate receptor gene in HL-60 cells.
Human leukemic HL-60 cells were treated with 1,25-dihydroxyvitamin D3 (VitD3) to induce monocytic cell differentiation. Concomitant with differentiation there was increased inositol-1,4,5-trisphosphate (InsP3) receptor expression, as assessed by both [3H]InsP3 binding site density and maximal InsP3-mediated Ca2+ mobilization from intracellular stores. Within 8 hr after VitD3 treatment the steady state level of a 10-kilobase InsP3 receptor mRNA was specifically elevated, and it continued to rise for 1-2 days. Nuclear run-off assays indicated a higher transcription rate of the InsP3 receptor gene in response to VitD3. The increased rate of transcription was sufficient to account for the increased steady state level of InsP3 receptor mRNA in VitD3-treated cells. VitD3 had no effect on the decay of InsP3 receptor mRNA in transcriptionally arrested cells; however, InsP3 receptor mRNA decay was dependent upon continued protein synthesis. Moreover, in cycloheximide-treated cells VitD3 was still able to induce an increase in the steady state level of InsP3 receptor mRNA, indicating that protein synthesis was not required for the enhanced transcriptional response. The results suggest that VitD3 directly enhances the transcription of the InsP3 receptor gene in HL-60 cells.
Bradford
P G
PG
Department of Pharmacology and Therapeutics, State University of New York, Buffalo 14214.
Jin
Y
Y
Hui
P
P
D001665:Binding Sites; D015152:Blotting, Northern; D002117:Calcitriol / Q000494:pharmacology*; D015220:Calcium Channels; D002454:Cell Differentiation / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D011061:Poly A / Q000032:analysis / Q000302:isolation & purification; D012313:RNA / Q000032:analysis / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D011061:Poly A; D012313:RNA; D015544:Inositol 1,4,5-Trisphosphate; D003513:Cycloheximide; D002117:Calcitriol