Anandamide-induced Ca2+ elevation leading to p38 MAPK phosphorylation and subsequent cell death via apoptosis in human osteosarcoma cells |
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Authors: | Hsu Shu-Shong Huang Chun-Jen Cheng He-Hsiung Chou Chiang-Ting Lee Hsiao-Ying Wang Jue-Long Chen I-Shu Liu Shiuh-Inn Lu Yih-Chau Chang Hong-Tai Huang Jong-Khing Chen Jin-Shyr Jan Chung-Ren |
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Institution: | Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan. |
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Abstract: | The effect of anandamide on human osteoblasts is unclear. This study examined the effect of anandamide on viability, apoptosis, mitogen-activated protein kinases (MAPKs) and Ca2+ levels in MG63 osteosarcoma cells. Anandamide at 50-200 microM decreased cell viability via apoptosis as demonstrated by propidium iodide staining and activation of caspase-3. Immunoblotting suggested that anandamide induced expression of ERK, JNK and p38 MAPK. Anandamide-induced cell death and apoptosis were reversed by SB203580, but not by PD98059 and SP600125, suggesting that anandamide's action was via p38 MAPK, but not via ERK and JNK. Anandamide at 1-100 microM induced Ca2+]i increases. Removal of extracellular Ca2+ decreased the anandamide response, indicating that anandamide induced Ca2+ influx and Ca2+ release. Chelation of intracellular Ca2+ with BAPTA reversed anandamide-induced cell death and p38 MAPK phosphorylation. Collectively, in MG63 cells, anandamide induced Ca2+]i increases which evoked p38 MAPK phosphorylation. This p38 MAPK phosphorylation subsequently activated caspase-3 leading to apoptosis. |
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Keywords: | Anandamide Apoptosis Ca2+ MAPKs MG63 cells p38 MAPK |
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