22-Oxacalcitriol upregulates p21(WAF1/Cip1) in human parathyroid glands. A preliminary report.
In the era of 22-oxacalcitriol (OCT), newly synthesized 1 alpha,25-dihydroxyvitamin D(3) analogue, against secondary hyperparathyroidism, the indications of parathyroidectomy (PTx) has been restricted. Recent investigations on animal models have revealed the inhibitory effects on PTH secretion after OCT treatment, whereas there has been no evidence about human parathyroid glands. A 38-year-old man with a 19-year history of hemodialysis was performed PTx after the failure of OCT treatment. Expressions of proliferative nuclear cell antigen (PCNA), calcium-sensing receptor (CaSR), vitamin D receptor (VDR), p53 and p21(WAF1/Cip1) were analyzed by Western blotting and immunohistochemistry on resected parathyroid glands. We confirmed up-regulations of CaSR and VDR, which contribute the reduction of serum PTH, by OCT treatment. Concomitant up-regulation of p21(WAF1/Cip1) but not p53, especially in nodular hyperplasia, can be considered to induce cell cycle arrest of the parathyroid cells, but not cytocidal effect of OCT.
Shiraishi
K
K
Department of Urology, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan. legal@po.cc.yamaguchi-u.ac.jp
Tsuchida
M
M
Wada
T
T
Yoshihiro
S
S
Takai
K
K
Suga
A
A
Kaneda
Y
Y
Naito
K
K
D000328:Adult; D015153:Blotting, Western; D002117:Calcitriol / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D010280:Parathyroid Glands / Q000378:metabolism*; D016105:Parathyroidectomy; D018167:Receptors, Calcitriol / Q000378:metabolism; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018167:Receptors, Calcitriol; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D016159:Tumor Suppressor Protein p53; D002117:Calcitriol