Lanthanum chloride bidirectionally influences calcification in bovine vascular smooth muscle cells.
Vascular calcification (VC) is frequent prevalence in patients with chronic kidney disease (CKD) and atherosclerosis. Lanthanum carbonate is used as an orally administered phosphate-binding agent to reduce the gastrointestinal absorption of phosphate and ameliorate VC in advanced CKD. In this study, we used bovine vascular smooth muscle cells as a model VC in vitro and studied the effects of lanthanum chloride on calcium deposition. Exposure of cells to LaCl(3) at the concentration of 0.1 µM suppressed the β-glycerophosphate-induced alkaline phosphatase activity and calcium deposition. Furthermore, LaCl(3) upregulated the β-glycerophosphate-suppressed expression of calcium-sensing receptor. In contrast to the inhibitory effect of LaCl(3) on calcium deposition, higher level lanthanum (50 µM) was found to promote immediately precipitation of calcium phosphate in cell culture medium. At this concentration, LaCl(3) was found to induce cell apoptosis which involves caspases-9 and -3. These data indicate that the promotory effect of LaCl(3) on calcium deposition is likely mediated by induction of apoptosis. Our in vitro findings do suggest that, in the context of raised lanthanum, greater attention should be paid to potential toxic effects associated to the use of lanthanide-based drugs.
Department of Chemical Biology, Capital Medical University School of Pharmaceutical Sciences, 10 Xitoutiao,You An Men, Beijing 100069, PR China.
Wen-Hua
WH
Zhao
Bao-Di
BD
Gou
Tian-Lan
TL
Zhang
Kui
K
Wang
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000150:complications / Q000378:metabolism; D002130:Calcium Phosphates / Q000737:chemistry / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D005994:Glycerophosphates / Q000494:pharmacology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism; D007811:Lanthanum / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010316:Particle Size; D044169:Receptors, Calcium-Sensing / Q000378:metabolism; D061205:Vascular Calcification / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*
D002130:Calcium Phosphates; D005994:Glycerophosphates; D044169:Receptors, Calcium-Sensing; C028521:lanthanum chloride; D007811:Lanthanum; C020243:calcium phosphate; D000469:Alkaline Phosphatase; D020169:Caspases; C031463:beta-glycerophosphoric acid