scholarly journals Calcium-Sensing Receptor Endocytosis Links Extracellular Calcium Signaling to Parathyroid Hormone-Related Peptide Secretion via a Rab11a-Dependent and AMSH-Sensitive Mechanism

2007 ◽  
Vol 21 (6) ◽  
pp. 1394-1407 ◽  
Author(s):  
Alma P. Reyes-Ibarra ◽  
Alejandro García-Regalado ◽  
Iliana Ramírez-Rangel ◽  
Ana L. Esparza-Silva ◽  
Margarita Valadez-Sánchez ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Calcium Signaling ◽  
Extracellular Calcium ◽  
Calcium Sensing Receptor ◽  
Receptor Endocytosis ◽  
Related Peptide ◽  
Calcium Sensing ◽  
Parathyroid Hormone Related Peptide ◽  
Peptide Secretion

Effects of calcium-sensing receptor on the secretion of parathyroid hormone-related peptide and its impact on humoral hypercalcemia of malignancy

2006 ◽  
Vol 290 (5) ◽  
pp. E761-E770 ◽  
Author(s):  
Naibedya Chattopadhyay
Keyword(s):  
Parathyroid Hormone ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Extracellular Calcium ◽  
Humoral Hypercalcemia Of Malignancy ◽  
Calcium Sensing Receptor ◽  
Humoral Hypercalcemia ◽  
Cellular Events ◽  
Calcium Sensing ◽  
Parathyroid Hormone Related Peptide

The extracellular calcium-sensing receptor (CaR) plays a key role in the defense against hypercalcemia by “sensing” extracellular calcium (Ca2+o) levels in the parathyroid and kidney, the key organs maintaining systemic calcium homeostasis. However, CaR function can be aberrant in certain pathophysiological states, e.g., in some types of cancers known to produce humoral hypercalcemia of malignancy (HHM) in humans and animal models in which high Ca2+o, via the CaR, produces a homeostatically inappropriate stimulation of parathyroid hormone-related peptide (PTHrP) secretion from these tumors. Increased levels of PTHrP set a cycle in motion whereby elevated systemic levels of Ca2+o resulting from its increased bone-resorptive and positive renal calcium-reabsorbing effects give rise to hypercalcemia, which in turn begets worsening hypercalcemia by stimulating further release of PTHrP by the cancer cells. I review the relationship between CaR activation and PTHrP release in normal and tumor cells giving rise to HHM and/or malignant osteolysis and the actions of the receptor on key cellular events such as proliferation, angiogenesis, and apoptosis of cancer cells that will favor tumor growth and osseous metastasis. I also illustrate diverse signaling mechanisms underlying CaR-stimulated PTHrP secretion and other cellular events in tumor cells. Finally, I raise several necessary questions to demonstrate the roles of the receptor in promoting tumors and metastases that will enable consideration of the CaR as a potential antagonizing/neutralizing target for the treatment of HHM.

scholarly journals A Case of a Giant Glucagonoma with Parathyroid Hormone-related Peptide Secretion Showing an Inconsistent Postsurgical Endocrine Status

2011 ◽  
Vol 50 (16) ◽  
pp. 1689-1694 ◽  
Author(s):  
Kiyokazu Shirai ◽  
Izumi Inoue ◽  
Jun Kato ◽  
Hiroki Maeda ◽  
Kosaku Moribata ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Related Peptide ◽  
Endocrine Status ◽  
Parathyroid Hormone Related Peptide ◽  
Peptide Secretion

Abstract 15371: Parathyroid Hormone-Related Peptide Protects Cardiomyocytes from Oxidative Stress: First Evidence of a Novel Endocrine-Cardiovascular Interaction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Sahiti Chukkapalli ◽  
Enbo Zhan ◽  
Robert Lasley ◽  
Nabanita S Datta
Keyword(s):  
Oxidative Stress ◽  
Parathyroid Hormone ◽  
Down Regulation ◽  
Akt Phosphorylation ◽  
Related Peptide ◽  
Viability Assay ◽  
Calcium Sensing ◽  
Mitogen Activated Protein ◽  
Added Benefit ◽  
Parathyroid Hormone Related Peptide

There is growing interest in the molecular cross-talk between the endocrine and cardiovascular systems, including the effects of hormones on cardiomyocte viability in models of ischemic and oxidative stress. However, current attention has focused on reproductive and metabolic hormones; the cardiac effects of calcium-regulating hormones (i.e., parathyroid hormone-related peptide (PTHrP)) have not been explored. To address this, we interrogated the effect of PTHrP on the viability of isolated adult mouse cardiomyocytes subjected to H 2 O 2 -induced oxidative stress. In Aim 1 , myocytes from wild type (WT) C57 mice were incubated for 16 hrs with 100 nM PTHrP or vehicle and exposed to 100 μM H 2 O 2 for 15 min. Myocyte viability was significantly improved in PTHrP-treated cells vs vehicle control (70±12% vs 20±15%; mean ± SD, p<0.01; Figure). Calcium sensing receptor and PTHrP signaling is purportedly associated with Mitogen-Activated Protein Kinases (MAPKs) and MAPK phosphatase-1 (MKP1). Accordingly, to achieve preliminary mechanistic insight into PTHrP-induced protection ( Aim 2 ), we: (i) incubated WT cardiomyocytes with PTHrP (100 nM) and probed for expression of MKP1; and (ii) repeated the viability assay as described above using myocytes from adult MKP1 knockout (KO) mice. Incubation of WT myocytes with PTHrP evoked a 55% decrease in MKP1 expression. Moreover, myocytes from MKP1 KO mice were resistant to oxidative injury: viability was maintained at 78±12% in vehicle controls (mean ± SD, p<0.01 vs the value of 20±15% in vehicle-treated WT cells), with no added benefit of PTHrP treatment (Figure). Finally ( Aim 3 ), in both models (PTHrP treatment; MKP1 KO), the enhanced cell viability was accompanied by ~2-fold increases in Akt phosphorylation. These data provide novel evidence that: i) down-regulation of MKP1 affords profound protection against oxidative stress; and ii) PTHrP is cardioprotective, possibly via down-regulation of MKP1 and activation of Akt signaling.

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