Calbindin-D28k (CaBP28k) identification and regulation by 1,25-dihydroxyvitamin D3 in human choriocarcinorna cell line JEG-3

Calbindin-D28k (CaBP28k) is a cytosolic calcium (Ca2(+))-binding protein expressed ill tissues such as intestine, kidneys and placenta. This protein is thought to be involved in Ca2(+) homeostasis. While it is well known that CaBP28k is influenced by 1,25-dihydroxyvitamin D-3[1,25(OH)(2)D-3] in the intestine and kidneys, nothing is known regarding the regulation of this protein in trophoblasts of human placenta. We used JEG-3 syncytiotrophoblast-like carcinoma cell line to study the regulation of CaBP28k in correlation with 1,25(OH)(2)D-3 receptor (VDR) following 1,25(OH)(2)D-3 treatments. Our data demonstrated for the first time that both CaBP28k mRNA and protein were highly induced by the addition of 1,25(OH)(2)D-3 in dose-dependent manner. Moreover, the increase and subsequent decrease in the expression of CaBP28k and VDR mRNAs indicates the transient nature of the changes in gene expression in response to 1,25(OH)(2)D-3. This is in contrast with the temporal pattern of increasing protein for CaBP28k and VDR. We also showed that new RNA and protein syntheses are required for 1,25(OH)(2)D-3-induced upregulation of CaBP28k. Furthermore, a 25-carboxylic ester analogue of 1,25(OH)(2)D-3, ZK159222, used as an antagonist of 1,25(OH)(2)D-3 signaling confirmed that indeed 1,25(OH)(2)D-3 was implicated in the induction of CaBP28k. These novel findings are a contribution to the processes that drive CaBP28k expression regulation in human placenta. (c) 2005 Elsevier Ireland Ltd. All rights reserved.