期刊
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 51, 期 4, 页码 1695-1709出版社
KARGER
DOI: 10.1159/000495674
关键词
Parathyroid hormone-related peptide; Intestinal epithelium cells; Calcium transport protein; Calcium uptake
资金
- National Natural Science Foundation [81170354]
- Guangdong Provincial Science and Technology Plan Fund [2011B031800195]
- Natural Science Foundation of Guangdong Province [S2012010009343]
- Department of Neurobiology
- Clinical Research Center of Nanfang Hospital
- Southern Medical University
Background/Aims: Parathyroid hormone-related protein (PTHrP) is implicated in regulating calcium homeostasis in vertebrates, including sea bream, chick, and mammals. However, the molecular mechanism underlying the function of PTHrP in regulating calcium transport is still not fully investigated. This study aimed to investigate the effect of PTHrP on the calcium uptake and its underlying molecular mechanism in rat enterocytes. Methods: The rat intestinal epithelial cell line (IEC-6) was used. Calcium uptake was determined by using the fluo-4 acetoxymethyl ester fluorescence method. The expression levels of RNAs and proteins was assessed by RT-PCR and Western-blot, respectively. Results: PTHrP (1-40) induced rapid calcium uptake in enterocytes in a dose-dependent manner. PTHrP (1-40) up-regulated parathyroid hormone 1 receptor (PTHR1) protein but not 1,25D3-MARRS receptor. Pretreatment of anti-PTHR1 antibody abolished the PTHrP (1-40)-induced calcium uptake. PTHrP (1-40) significantly up-regulated four transcellular calcium transporter proteins, potential vanilloid member 6 (TRPV6), calbindin-D9k (CaBP-D9k), sodium-calcium exchanger 1 (NCX1) and plasma membrane calcium ATPase 1 (PMCA1), in a dose-and time-dependent manner. Pre-treatment with TRPV6 or CaBP-D9k antibodies or knockout of rat TRPV6 or CaBP-D9k markedly inhibited PTHrP (1-40)-induced calcium uptake, whereas inhibition of NCX or PMCA1 by antibodies or inhibitors had no effect on PTHrP(1-40)-induced calcium uptake. Furthermore, PTHrP (1-40) treatment up-regulated protein levels of protein kinase C (PKC alpha/beta) and protein kinase A (PKA). Pretreatment of PKC alpha/beta inhibitor (but not PKA inhibitor) inhibited PTHrP (1-40)-induced calcium uptake. Conclusion: PTHrP (1-40) stimulates calcium uptake via PTHR1 receptor and PKC alpha/beta signaling pathway in rat enterocytes, and calcium transporters TRPV6 and CaBP-D9k are necessary for this stimulatory effect. (c) 2018 The Author(s) Published by S. Karger AG, Basel
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