Altered vitamin D metabolism and receptor interaction with the target genes in renal failurecalcitriol receptor interaction with its target gene in renal failure
作者:
Chen Hsu,
Sanjeevkumar Patel,
期刊:
Current Opinion in Nephrology and Hypertension
(OVID Available online 1995)
卷期:
Volume 4,
issue 4
页码: 302-306
ISSN:1062-4821
年代: 1995
出版商: OVID
数据来源: OVID
摘要:
The genomic action of calcitriol is mediated through the interaction of the calcitriol receptor (VDR) with the vitamin D response elements of the target genes. Although decreased VDR concentration in renal failure could diminish the biological action of calcitriol, recent study indicates that uremic toxins could modify the VDR DNA-binding domain and inhibit the binding of the VDR to the vitamin D response elements. The latter reaction could also account for end-organ resistance in renal failure. The inhibitory action of uremic toxins has been testedin vivoby a method using gene transcription. It was demonstrated that uremic ultrafiltrate blocks calcitriol-induced chloramphenical acetyltransferase reporter constructs containing a synthetic vitamin D response element in JEG-3 cells. Taken together, the findings indicate that uremia could underlie the calcitriol resistance in renal failure. The modification of the VDR may involve Schiff base formation between lysine residues of the VDR DNA-binding domain and reactive aldehydes accumulated in uremia. This suggestion is on the basis of the finding that the VDR and other steroid receptors form Schiff bases with pyridoxal 5′-phosphate and weaken the binding of these receptors to the DNA cellulose.
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