Calcium Nutrition and Extracellular Calcium Sensing: Relevance for the Pathogenesis of Osteoporosis, Cancer and Cardiovascular DiseasesReport as inadecuate




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Department of Pathophysiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria





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Abstract Through a systematic search in Pubmed for literature, on links between calcium malnutrition and risk of chronic diseases, we found the highest degree of evidence for osteoporosis, colorectal and breast cancer, as well as for hypertension, as the only major cardiovascular risk factor. Low calcium intake apparently has some impact also on cardiovascular events and disease outcome. Calcium malnutrition can causally be related to low activity of the extracellular calcium-sensing receptor CaSR. This member of the family of 7-TM G-protein coupled receptors allows extracellular Ca2+ to function as a -first messenger- for various intracellular signaling cascades. Evidence demonstrates that Ca2+-CaSR signaling in functional linkage with vitamin D receptor VDR-activated pathways i promotes osteoblast differentiation and formation of mineralized bone; ii targets downstream effectors of the canonical and non-canonical Wnt pathway to inhibit proliferation and induce differentiation of colorectal cancer cells; iii evokes Ca2+ influx into breast cancer cells, thereby activating pro-apoptotic intracellular signaling. Furthermore, Ca2+-CaSR signaling opens Ca2+-sensitive K+ conductance channels in vascular endothelial cells, and also participates in IP3-dependent regulation of cytoplasmic Ca2+, the key intermediate of cardiomyocyte functions. Consequently, impairment of Ca2+-CaSR signaling may contribute to inadequate bone formation, tumor progression, hypertension, vascular calcification and, probably, cardiovascular disease. View Full-Text

Keywords: Calcium intake; calcium-sensing receptor; Wnt signaling; vitamin D; bone formation; colorectal cancer; breast cancer; hypertension; vasculature; cardiac functions Calcium intake; calcium-sensing receptor; Wnt signaling; vitamin D; bone formation; colorectal cancer; breast cancer; hypertension; vasculature; cardiac functions





Author: Meinrad Peterlik * , Enikoe Kállay and Heide S. Cross

Source: http://mdpi.com/



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