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The negative effect of dexamethasone on calcium-processing gene expressions is associated with a glucocorticoid-induced calcium-absorbing disorder
- Source :
-
Life Sciences . Jul2009, Vol. 85 Issue 3/4, p146-152. 7p. - Publication Year :
- 2009
-
Abstract
- Abstract: Aims: Although dexamethasone (Dex) is used widely as an anti-inflammatory and immunosuppressive drug, Dex appears to have severe side-effects, including osteoporosis. This study determined the effects of Dex on duodenal and renal expressions of the calcium-processing genes transient receptor potential cation channel, subfamily V, member 5/6 (TRPV5/6), calbindin-D9k/-D28k (CaBP-9k/28k), Na+/Ca2+ exchanger 1 (NCX1), and plasma membrane Ca2+-ATPase (PMCA) 1b. Main methods: Mice were injected subcutaneously with Dex for 1 or 5 days. The mRNA and protein expression levels of these calcium-processing genes were measured by real-time PCR and immunohistochemistry/immunoblot analysis, respectively. In addition, serum parathyroid hormone (PTH) levels were measured following Dex treatments. Key findings: Treatment with Dex for 24 h resulted in the inductions of duodenal TRPV6, CaBP-9k and PMCA1b transcripts and renal TRPV5, CaBP-9k, and NCX1 transcripts, while it reduced the transcription of renal TRPV6. Although the expressional changes were weak, duodenal expressions of glucocorticoid receptor (GR), the vitamin D receptor (VDR), and renal expressions of the parathyroid hormone receptor (PTHR) and VDR were increased following 24 h treatment with Dex. A five-day treatment with Dex reduced the transcriptional levels of duodenal TRPV6 and CaBP-9k by 60%. Transcripts for VDR and GR in the duodenum increased marginally. Significance: These results suggest that the expressions of TRPV6 and CaBP-9k in the duodenum appear to be a major regulatory target for glucocorticoids (GCs), and may be involved in the negative regulation of calcium absorption in GC-induced osteoporosis (GIO). The transcriptional regulation of TRPV6 and CaBP-9k in the duodenum seems complex given that there is an increase at 1-day treatment followed by a decrease at 5-day treatment. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 00243205
- Volume :
- 85
- Issue :
- 3/4
- Database :
- Academic Search Index
- Journal :
- Life Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 42966864
- Full Text :
- https://doi.org/10.1016/j.lfs.2009.05.013