scholarly journals Parathyroid Hormone-Related Protein (1-40) Enhances Calcium Uptake in Rat Enterocytes Through PTHR1 Receptor and Protein Kinase Cα/β Signaling

2018 ◽  
Vol 51 (4) ◽  
pp. 1695-1709
Author(s):  
Cuiping Liu ◽  
Guoli Shao ◽  
Yirong Lu ◽  
Minmin Xue ◽  
Fenfen Liang ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Protein Kinase ◽  
Molecular Mechanism ◽  
Calcium Uptake ◽  
Dependent Manner ◽  
Related Protein ◽  
Acetoxymethyl Ester ◽  
Parathyroid Hormone Related Protein ◽  
Pre Treatment ◽  
Rat Enterocytes

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. Pre-treatment 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 α/β) and protein kinase A (PKA). Pretreatment of PKC α/β inhibitor (but not PKA inhibitor) inhibited PTHrP (1-40)-induced calcium uptake. Conclusion: PTHrP (1-40) stimulates calcium uptake via PTHR1 receptor and PKC α/β signaling pathway in rat enterocytes, and calcium transporters TRPV6 and CaBP-D9k are necessary for this stimulatory effect.

scholarly journals Parathyroid hormone-related protein regulates intestinal calcium transport in sea bream (Sparus auratus)

2006 ◽  
Vol 291 (5) ◽  
pp. R1499-R1506 ◽  
Author(s):  
Juan Fuentes ◽  
Joana Figueiredo ◽  
Deborah M. Power ◽  
Adelino V. M. Canário
Keyword(s):  
Parathyroid Hormone ◽  
Calcium Transport ◽  
Calcium Uptake ◽  
Sea Bream ◽  
Whole Body ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Intestinal Calcium Transport ◽  
Sparus Auratus

Parathyroid hormone-related protein (PTHrP) is a factor associated with normal development and physiology of the nervous, cardiovascular, immune, reproductive, and musculoskeletal systems in higher vertebrates. It also stimulates whole body calcium uptake in sea bream ( Sparus auratus) larvae with an estimated 60% coming from intestinal uptake in seawater. The present study investigated the role of PTHrP in the intestinal calcium transport in the sea bream in vitro. Unidirectional mucosal-to-serosal and serosal-to-mucosal 45Ca fluxes were measured in vitro in duodenum, hindgut, and rectum mounted in Ussing chambers. In symmetric conditions with the same saline, bathing apical and basolateral sides of the preparation addition of piscine PTHrP 1–34 (6 nM) to the serosal surface resulted in an increase in mucosal to serosal calcium fluxes in duodenum and hindgut and a reduction in serosal to mucosal in the rectum, indicating that different mechanisms are responsive to PTHrP along the intestine. In control asymmetric conditions, with serosal normal and mucosal bathed with a saline similar in composition to the intestinal fluid, there was a net increase in calcium uptake in all regions. The addition of 6 nM PTHrP 1–34 increased net calcium uptake two- to threefold in all regions. The stimulatory effect of PTHrP on net intestinal calcium absorption is consistent with a hypercalcemic role for the hormone. The results support the view that PTHrP, alone or in conjunction with recently identified PTH-like peptides, counteracts in vivo the hypocalcemic effects of stanniocalcin.

scholarly journals Parathyroid hormone-related protein-stanniocalcin antagonism in regulation of bicarbonate secretion and calcium precipitation in a marine fish intestine

2010 ◽  
Vol 299 (1) ◽  
pp. R150-R158 ◽  
Author(s):  
Juan Fuentes ◽  
Deborah M. Power ◽  
Adelino V. M. Canário
Keyword(s):  
Parathyroid Hormone ◽  
Marine Fish ◽  
Calcium Uptake ◽  
Sea Bream ◽  
Bicarbonate Secretion ◽  
Related Protein ◽  
Calcium Efflux ◽  
Parathyroid Hormone Related Protein ◽  
Calcium Availability ◽  
Calcium Precipitation

Bicarbonate secretion in the intestine (duodenum) of marine fish has been suggested to play a major role in regulation of calcium availability for uptake. However, while the end process may lead to carbonate precipitation, regulation of transport of calcium and/or bicarbonate may actually result in fine-tuning of calcium availability for transport. To test this hypothesis, sea bream ( Sparus auratus ) duodenal preparations were mounted in Ussing-type chambers and the effect of parathyroid hormone-related protein (PTHrP) and stanniocalcin 1 (STC 1) on the control of intestinal bicarbonate secretion and calcium transport was analyzed. As expected, PTHrP increased net calcium uptake, as a result of an increase of calcium uptake without changes in calcium efflux. In contrast, purified sea bream STC 1 caused a minor decrease of calcium uptake and a two- to threefold increase in calcium efflux. As a result, STC 1 was able to invert the calcium flux from net calcium uptake to net calcium loss, which is in keeping with its known actions as a hypocalcemic factor. Furthermore, both PTHrP and STC 1 regulate intestinal bicarbonate secretion. PTHrP increased calcium uptake and simultaneously reduced the single factor that induces calcium precipitation, bicarbonate secretion. In contrast, STC 1, while reversing the calcium net flux to make it secretory, promoted intestinal bicarbonate secretion, both actions directed to decrease the calcium gradient across the epithelium and promote immobilization in the form of bicarbonate in the intestinal lumen. Together our results provide robust evidence to support an antagonistic action of PTHrP and STC 1 in the fine control of movements of both calcium and bicarbonate in the intestine of seawater fish.

Protein kinase C-activating domains of parathyroid hormone-related protein

2009 ◽  
Vol 8 (4) ◽  
pp. 497-503 ◽  
Author(s):  
Lyne Gagnon ◽  
Hervé Jouishomme ◽  
James F. Whitfield ◽  
Jon P. Durkin ◽  
Susanne MacLean ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Parathyroid Hormone ◽  
Protein Kinase ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Kinase C

Effects of parathyroid hormone-related protein on human mesangial cells in culture

1999 ◽  
Vol 277 (6) ◽  
pp. E990-E995 ◽  
Author(s):  
Ricardo J. Bosch ◽  
Pilar Rojo-Linares ◽  
Guadalupe Torrecillas-Casamayor ◽  
M. Carmen Iglesias-Cruz ◽  
Diego Rodríguez-Puyol ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Mesangial Cells ◽  
Biological Effects ◽  
Human Kidney ◽  
Kidney Cortex ◽  
Dependent Manner ◽  
Related Protein ◽  
Human Mesangial Cells ◽  
Parathyroid Hormone Related Protein ◽  
Pthrp Receptor

Parathyroid hormone (PTH) and PTH-related protein (PTHrP) produce similar biological effects through the PTH/PTHrP receptor. Because PTHrP exhibits vasodilatory properties, we evaluated the hypothesis that this hormone interacts with human mesangial cells (HMC). The PTHrP prevented both the expected reduction in the planar cell surface area and the increase in myosin light-chain phosphorylation induced by platelet-activating factor (PAF) on HMC, in a dose-dependent manner. This effect was completely blocked by pertussis toxin and dideoxyadenosine, suggesting that a G protein-coupled receptor and cAMP are important in the PTHrP transduction mechanism. Moreover, PTHrP increased cAMP synthesis and thymidine incorporation in HMC. However, whereas RT-PCR and Southern and Northern blot analyses demonstrated the expression of human PTH/PTHrP receptor in human kidney cortex, no expression could be demonstrated in HMC. These results show that PTH and PTHrP directly interact with mesangial cells. These effects might be mediated by a receptor different from the PTH/PTHrP receptor.

scholarly journals Parathyroid Hormone-Related Protein (107-139) Stimulates Interleukin-6 Expression in Human Osteoblastic Cells

1999 ◽  
Vol 10 (4) ◽  
pp. 796-803
Author(s):  
FERNANDO DE MIGUEL ◽  
PILAR MARTINEZ-FERNANDEZ ◽  
CARLOS GUILLEN ◽  
ALVARO VALIN ◽  
ANA RODRIGO ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Protein Kinase ◽  
Interleukin 6 ◽  
Osteoblastic Cells ◽  
Protein Synthesis Inhibitor ◽  
Related Protein ◽  
Synthesis Inhibitor ◽  
Parathyroid Hormone Related Protein ◽  
Protein Kinase C Inhibitor ◽  
Human Osteoblastic Cells

Abstract. The N-terminal region of both parathyroid hormone (PTH) and PTH-related protein (PTHrP) binds to the same PTH/PTHrP receptor in osteoblasts. However, C-terminal PTHrP (107-139) inhibits growth and various functions of osteoblasts and osteoclasts apparently through PTHrP-specific receptors. PTH (1-34) and PTHrP (1-34) rapidly induce interleukin-6 (IL-6) expression by osteoblasts. The aim of the present study was to assess the effects of PTHrP (107-139) on IL-6 gene expression and secretion by osteoblastic cells from human trabecular bone (hOB). Using reverse transcription followed by PCR, it was found that IL-6 mRNA was twofold maximally increased by either PTHrP (1-34) or PTHrP (107-139), at 10 nM, over basal within 1 to 2 h in hOB cells. This effect of PTHrP (107-139), and that of PTHrP (1-34), were abolished by the transcription inhibitor actinomycin D. Meanwhile, puromycin, a protein synthesis inhibitor, superinduced IL-6 expression in the presence or absence of each PTHrP peptide. Both PTHrP (1-34) and PTHrP (107-139), but not PTHrP (38-64), stimulated IL-6 secretion to the hOB cell-conditioned medium at 24 h, dose dependently. In addition, this maximal stimulatory effect (twofold over basal) was similar with each PTHrP peptide alone, and not additive when added together. PTHrP (107-139) stimulation of mRNA and protein in hOB cells was abolished by bisindolylmaleimide I, a protein kinase C inhibitor, but not by either adenosine 3′,5′-cyclic monophosphorothioate, Rp-isomer (Rp-cAMPS), or N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H89), two protein kinase A inhibitors. These results indicate that C-terminal PTHrP, like its N-terminal domain, induces IL-6 production by human osteoblastic cells. This effect of both PTHrP regions could provide a mechanism to modulate bone turnover.

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