Down-regulation of L-type Ca2+ channel transcript levels by 1,25-dihydroxyvitamin D-3 - Osteoblastic cells express L-type alpha(1C) Ca2+ channel isoforms

被引:33
作者
Meszaros, JG [1 ]
Karin, NJ [1 ]
Akanbi, K [1 ]
FarachCarson, MC [1 ]
机构
[1] UNIV TEXAS, DENT BRANCH, DEPT BASIC SCI, HOUSTON, TX 77030 USA
关键词
D O I
10.1074/jbc.271.51.32981
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Osteoblast Ca2+ channels play a fundamental role in controlling intracellular and systemic Ca2+ homeostasis. A reverse transcription-polymerase chain reaction strategy was used to determine the molecular identity of voltage-sensitive calcium channels present in ROS 17/2.8 osteosarcoma cells. The amino acid sequences encoded by the two resultant PCR products matched the alpha 1(C-a) and the alpha 1(C-d) isoforms. The ability of 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) and structural analogs to modulate expression of voltage-sensitive calcium channel mRNA transcripts was then investigated. ROS 17/2.8 cells were cultured for 48 h in the presence of either 1,25(OH)(2)D-3, 1,24-dihydroxy-22-ene-24-cyclopropyl D-3 (analog BT) or 25-hydroxy-16-ene-23-yne-D-3 (analog AT), and the levels of mRNA encoding alpha(1C) were quantitated using a competitive reverse transcription-polymerase chain reaction assay. We found that 1,25(OH)(2)D-3 and analog BT reduced steady state levels of alpha(1C) mRNA. Conversely, the Ca2+-mobilizing analog AT did not alter steady state levels of voltage-sensitive calcium channel mRNA. Since analog BT, but not analog AT, binds and transcriptionally activates the nuclear receptor for 1,25(OH)(2)D-3, these findings suggest that the down-regulation of voltage-sensitive calcium channel mRNA levels may involve the nuclear receptor.
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页码:32981 / 32985
页数:5
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