Effects of MgCl 2 on the release and recycling of heparan sulfate proteoglycans in a rat parathyroid cell line

Abstract

Divalent cations, such as Mg 2+, Ba 2+, and Co 2+, are known to mimic the effects of Ca 2+ in parathyroid cells, but it is not clear whether the mechanism of their action is the same as that of Ca 2+. We have shown that extracellular Ca 2+ concentration ([Ca 2+] e) regulates the distribution and recycling of cell-surface heparan sulfate (HS) proteoglycans in a rat parathyroid cell line; at normal to high [Ca 2+] e (e.g., 2 m m) HS proteoglycans are primarily localized intracellularly, while at low [Ca 2+] e (0.05 m m) they are translocated to the cell surface and rapidly recycle (Takeuchi, Y., Sakaguchi, K., Yanagishita, M., Aurbach, G. D., and Hascall, V. C., 1990, J. Biol. Chem. 265, 13661–13668). We now show that a high concentration of Mg 2+ (8 m m) reduces the amount of recycling HS proteoglycans in low [Ca 2+] e. However, the primary effects of high Ca 2+ and high Mg 2+ on the recycling HS proteoglycans are different. High [Ca 2+] e causes translocation of HS proteoglycans to intracellular compartments, while high Mg 2+ stimulates cleavage of their core proteins and subsequent shedding of HS proteoglycans into the medium, thereby depleting the recycling molecules. However, high Mg 2+ does not induce shedding of HS proteoglycans in high [Ca 2+] e. The effects of Ba 2+ and Co 2+ were similar to those of Mg 2+, but Sr 2+ showed no significant effects on HS proteoglycan translocation. Otherwise, 8 m m Mg 2+ did not alter biosynthesis or intracellular catabolism of HS proteoglycans. These observations suggest that the recycling of HS proteoglycans in parathyroid cells is sensitive only to [Ca 2+] e, whereas several other divalent cations can deplete the recycling HS proteoglycans by a distinctly different mechanism. Thus, the mechanism by which Ca 2+ regulates the amounts of the recycling HS proteoglycans may be more physiological and play a functional role in parathyroid Cells.