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Characterization of insulin-like growth factor I regulation of renal 25-hydroxyvitamin D3 1-alpha hydroxylase in aging

By Wan-ping Lai


xx, 149 leaves : ill. ; 30 cm.PolyU Library Call No.: [THS] LG51 .H577M ABCT 2003 LaiPhosphate (P) is a known regulator in 1, 25-(OH)2D3 metabolism. IGF-I peptide is also known to regulate l,25-(OH)2D3 production. In this study, it was hypothesized that the regulation of IGF-I axis during dietary P restriction was responsible for the regulation of a key enzyme, renal 25-hydroxyvitamin D3 1-alpha hydroxylase (1-OHase), in vitamin D metabolism. Part of the IGF-I axis was studied, including two receptor proteins, insulin-like growth factor 1 receptor (IGFTR), insulin receptor (IR), and two docking proteins, Src-homology collagen (Shc) and insulin receptor substrate-I (IRS-1). Male Sprague Dawley rats aged 4 to 8 weeks and 8 to 12 weeks were used in the study as young and adult animal models, respectively. Rats were fed with either a normal (NPD, 0.65 % P, 0.60 % Ca) or a low (LPD; 0.1% P, 0.60% Ca) phosphate diet for 0, 1, 2, 3, 5 and 7 days. In young rats, the expression of 1-OHase as well as the receptors in IGF-I axis in renal proximal tubules were up-regulated in response to LPD. The up-regulation of 1-OHase protein was caused by an enhancement of in vivo protein stability. However, this mechanism does not apply to the regulation of receptor proteins in IGF-I axis in young rats. In adult rats, LPD did not alter the expression of 1-OHase protein in renal proximal tubules, but proteins in the IGF-I axis, including both the receptors and docking proteins, were up-regulated during LPD. In addition, the responsiveness to LPD in the IGF-I axis was found to be greater than in young rats. In the in vivo study, LPD did not enhance receptor protein stability. These findings showed that regulations of proteins in IGF-I axis and 1-OHase by LPD were age-dependent and their regulations were not operated by the same mechanism, i.e. an enhancement of in vivo protein stability. In the present study, some serum measurements were performed, including P, Ca, 1, 25-(OH)2D3 and LGF-I. Dietary P restriction decreased the serum P levels in both young and adult rats, but showed no effect in serum Ca content. Serum 1, 25-(OH)2D3 level increased significantly by LPD in both age groups. However, serum IGF-I level was found to be decreased in young rats, but increased in adult rats during 7 days of LPD treatment. Results were correlated between serum P level and different protein expressions in young rats. It was found that serum P level was inversely related with renal 1-OHase, IGFIR and IR protein expressions in young rats. In particular, correlations of 1-OHase and IR proteins with the change in serum P level were very similar. Besides, 1-OHase showed a greater positive relationship with IR protein expression than with IGFIR, suggesting that IR was preferably involved in renal 1-OHase protein regulation.Department of Applied Biology and Chemical TechnologyM.Phil., Dept. of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, 200

Topics: Osteoporosis, Older people -- Health and hygiene -- China -- Hong Kong, Hong Kong Polytechnic University -- Dissertations
Publisher: The Hong Kong Polytechnic University
Year: 2003
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