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Desipramine-induced Ca-independent apoptosis in Mg63 human osteosarcoma cells: dependence on P38 mitogen-activated protein kinase-regulated activation of caspase 3.
Clin Exp Pharmacol Physiol. 2009 Mar; 36(3):297-303.CE

Abstract

1. It has been shown that the antidepressant desipramine is able to induce increases in [Ca(2+)](i) and cell death in MG63 human osteosacroma cells, but whether apoptosis is involved is unclear. In the present study, the effect of desipramine on apoptosis and the underlying mechanisms were explored. It was demonstrated that desipramine induced cell death in a concentration- and time-dependent manner. 2. Cells treated with 100-800 mmol/L desipramine showed typical apoptotic features, including an increase in sub-diploid nuclei and activation of caspase 3, indicating that these cells underwent apoptosis. Immunoblotting revealed that 100 mmol/L desipramine activated extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). Although pretreatment of cells with 20 mmol/L PD98059 (an ERK inhibitor) or 20 mmol/L SP600125 (an inhibitor of JNK) did not inhibit cell death, the addition of 20 mmol/L SB203580 (a p38 MAPK inhibitor) partially rescued cells from apoptosis. Desipramine-induced caspase 3 activation required p38 MAPK activation. 3. Pretreatment of cells with BAPTA/AM (20 mmol/L) to prevent desipramine-induced increases in [Ca(2+)](i) did not protect cells from death. 4. The results of the present study suggest that, in MG63 human osteosarcoma cells, desipramine causes Ca(2+)-independent apoptosis by inducing p38 MAPK-associated activation of caspase 3.

Authors+Show Affiliations

Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18986328

Citation

Lu, Ti, et al. "Desipramine-induced Ca-independent Apoptosis in Mg63 Human Osteosarcoma Cells: Dependence On P38 Mitogen-activated Protein Kinase-regulated Activation of Caspase 3." Clinical and Experimental Pharmacology & Physiology, vol. 36, no. 3, 2009, pp. 297-303.
Lu T, Huang CC, Lu YC, et al. Desipramine-induced Ca-independent apoptosis in Mg63 human osteosarcoma cells: dependence on P38 mitogen-activated protein kinase-regulated activation of caspase 3. Clin Exp Pharmacol Physiol. 2009;36(3):297-303.
Lu, T., Huang, C. C., Lu, Y. C., Lin, K. L., Liu, S. I., Wang, B. W., Chang, P. M., Chen, I. S., Chen, S. S., Tsai, J. Y., Chou, C. T., & Jan, C. R. (2009). Desipramine-induced Ca-independent apoptosis in Mg63 human osteosarcoma cells: dependence on P38 mitogen-activated protein kinase-regulated activation of caspase 3. Clinical and Experimental Pharmacology & Physiology, 36(3), 297-303. https://doi.org/10.1111/j.1440-1681.2008.05065.x
Lu T, et al. Desipramine-induced Ca-independent Apoptosis in Mg63 Human Osteosarcoma Cells: Dependence On P38 Mitogen-activated Protein Kinase-regulated Activation of Caspase 3. Clin Exp Pharmacol Physiol. 2009;36(3):297-303. PubMed PMID: 18986328.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Desipramine-induced Ca-independent apoptosis in Mg63 human osteosarcoma cells: dependence on P38 mitogen-activated protein kinase-regulated activation of caspase 3. AU - Lu,Ti, AU - Huang,Chorng-Chih, AU - Lu,Yih-Chau, AU - Lin,Ko-Long, AU - Liu,Shiuh-In, AU - Wang,Being-Whey, AU - Chang,Po-Min, AU - Chen,I-Shu, AU - Chen,Sheng-Shih, AU - Tsai,Jeng-Yu, AU - Chou,Chiang-Ting, AU - Jan,Chung-Ren, Y1 - 2008/10/15/ PY - 2008/11/7/pubmed PY - 2009/5/29/medline PY - 2008/11/7/entrez SP - 297 EP - 303 JF - Clinical and experimental pharmacology & physiology JO - Clin Exp Pharmacol Physiol VL - 36 IS - 3 N2 - 1. It has been shown that the antidepressant desipramine is able to induce increases in [Ca(2+)](i) and cell death in MG63 human osteosacroma cells, but whether apoptosis is involved is unclear. In the present study, the effect of desipramine on apoptosis and the underlying mechanisms were explored. It was demonstrated that desipramine induced cell death in a concentration- and time-dependent manner. 2. Cells treated with 100-800 mmol/L desipramine showed typical apoptotic features, including an increase in sub-diploid nuclei and activation of caspase 3, indicating that these cells underwent apoptosis. Immunoblotting revealed that 100 mmol/L desipramine activated extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). Although pretreatment of cells with 20 mmol/L PD98059 (an ERK inhibitor) or 20 mmol/L SP600125 (an inhibitor of JNK) did not inhibit cell death, the addition of 20 mmol/L SB203580 (a p38 MAPK inhibitor) partially rescued cells from apoptosis. Desipramine-induced caspase 3 activation required p38 MAPK activation. 3. Pretreatment of cells with BAPTA/AM (20 mmol/L) to prevent desipramine-induced increases in [Ca(2+)](i) did not protect cells from death. 4. The results of the present study suggest that, in MG63 human osteosarcoma cells, desipramine causes Ca(2+)-independent apoptosis by inducing p38 MAPK-associated activation of caspase 3. SN - 1440-1681 UR - https://www.unboundmedicine.com/medline/citation/18986328/Desipramine_induced_Ca_independent_apoptosis_in_Mg63_human_osteosarcoma_cells:_dependence_on_P38_mitogen_activated_protein_kinase_regulated_activation_of_caspase_3_ L2 - https://doi.org/10.1111/j.1440-1681.2008.05065.x DB - PRIME DP - Unbound Medicine ER -