Tags

Type your tag names separated by a space and hit enter

Activation of c-Jun N-terminal protein kinase is a common mechanism underlying paraquat- and rotenone-induced dopaminergic cell apoptosis.
Toxicol Sci. 2007 May; 97(1):149-62.TS

Abstract

Parkinson's disease (PD) is characterized by selective loss of dopaminergic neurons in the substantia nigra of the brain. Although the underlying causes are not well characterized, epidemiological studies suggest an elevated risk of PD with occupational pesticide exposure. Here, we utilized pheochromocytoma (PC) 12 and SH-SY5Y cells as well as rat primary cultured dopaminergic neurons to investigate mechanisms for dopaminergic cell death induced by paraquat and rotenone, pesticides that are used to model PD in rodents. Both paraquat and rotenone induce selective loss of dopaminergic neurons in primary cultures. We discovered that paraquat induces apoptosis in PC12 cells but not in SH-SY5Y cells, while rotenone exposure causes apoptosis in SH-SY5Y cells but not in PC12 cells. The selective ability of paraquat and rotenone to induce apoptosis in different cell lines correlates with their ability to activate c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinases. Furthermore, JNK and p38 are required for rotenone-induced apoptosis in SH-SY5Y cells (K. Newhouse et al., 2004, Toxicol. Sci. 79, 137-146) as well as primary neurons, and for paraquat-induced apoptosis in PC12 cells. However, JNK but not p38 plays a role in paraquat-induced loss of primary cultured dopaminergic neurons. Our data identify JNK activation as a common mechanism underlying dopaminergic cell death induced by both paraquat and rotenone in model cell lines and primary cultures.

Authors+Show Affiliations

Toxicology Program in the Department of Environmental & Occupational Health Sciences, University of Washington, Seattle, Washington 98195-7234, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17324951

Citation

Klintworth, Heather, et al. "Activation of c-Jun N-terminal Protein Kinase Is a Common Mechanism Underlying Paraquat- and Rotenone-induced Dopaminergic Cell Apoptosis." Toxicological Sciences : an Official Journal of the Society of Toxicology, vol. 97, no. 1, 2007, pp. 149-62.
Klintworth H, Newhouse K, Li T, et al. Activation of c-Jun N-terminal protein kinase is a common mechanism underlying paraquat- and rotenone-induced dopaminergic cell apoptosis. Toxicol Sci. 2007;97(1):149-62.
Klintworth, H., Newhouse, K., Li, T., Choi, W. S., Faigle, R., & Xia, Z. (2007). Activation of c-Jun N-terminal protein kinase is a common mechanism underlying paraquat- and rotenone-induced dopaminergic cell apoptosis. Toxicological Sciences : an Official Journal of the Society of Toxicology, 97(1), 149-62.
Klintworth H, et al. Activation of c-Jun N-terminal Protein Kinase Is a Common Mechanism Underlying Paraquat- and Rotenone-induced Dopaminergic Cell Apoptosis. Toxicol Sci. 2007;97(1):149-62. PubMed PMID: 17324951.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of c-Jun N-terminal protein kinase is a common mechanism underlying paraquat- and rotenone-induced dopaminergic cell apoptosis. AU - Klintworth,Heather, AU - Newhouse,Kathleen, AU - Li,Tingting, AU - Choi,Won-Seok, AU - Faigle,Roland, AU - Xia,Zhengui, Y1 - 2007/02/25/ PY - 2007/2/28/pubmed PY - 2007/7/4/medline PY - 2007/2/28/entrez SP - 149 EP - 62 JF - Toxicological sciences : an official journal of the Society of Toxicology JO - Toxicol Sci VL - 97 IS - 1 N2 - Parkinson's disease (PD) is characterized by selective loss of dopaminergic neurons in the substantia nigra of the brain. Although the underlying causes are not well characterized, epidemiological studies suggest an elevated risk of PD with occupational pesticide exposure. Here, we utilized pheochromocytoma (PC) 12 and SH-SY5Y cells as well as rat primary cultured dopaminergic neurons to investigate mechanisms for dopaminergic cell death induced by paraquat and rotenone, pesticides that are used to model PD in rodents. Both paraquat and rotenone induce selective loss of dopaminergic neurons in primary cultures. We discovered that paraquat induces apoptosis in PC12 cells but not in SH-SY5Y cells, while rotenone exposure causes apoptosis in SH-SY5Y cells but not in PC12 cells. The selective ability of paraquat and rotenone to induce apoptosis in different cell lines correlates with their ability to activate c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinases. Furthermore, JNK and p38 are required for rotenone-induced apoptosis in SH-SY5Y cells (K. Newhouse et al., 2004, Toxicol. Sci. 79, 137-146) as well as primary neurons, and for paraquat-induced apoptosis in PC12 cells. However, JNK but not p38 plays a role in paraquat-induced loss of primary cultured dopaminergic neurons. Our data identify JNK activation as a common mechanism underlying dopaminergic cell death induced by both paraquat and rotenone in model cell lines and primary cultures. SN - 1096-6080 UR - https://www.unboundmedicine.com/medline/citation/17324951/Activation_of_c_Jun_N_terminal_protein_kinase_is_a_common_mechanism_underlying_paraquat__and_rotenone_induced_dopaminergic_cell_apoptosis_ L2 - https://academic.oup.com/toxsci/article-lookup/doi/10.1093/toxsci/kfm029 DB - PRIME DP - Unbound Medicine ER -