Abstract
Cd induces oxidative stress and apoptosis in various cells by activating mitogen-activated protein kinases (MAPKs), but the precise signaling components of the MAPK cascade and their role in neuronal apoptosis are still unclear. Here, we report that Cd treatment of SH-SY5Y cells caused apoptosis through sequential phosphorylation of the apoptosis signal regulating kinase 1, MAPK kinase 4, c-Jun N-terminal kinase (JNK), and c-Jun as determined by overexpression of dominant negative (DN) constructs of these genes or using a specific JNK inhibitor SP600125. Both Cd-induced JNK and c-Jun phosphorylation and apoptosis were inhibited dramatically by N-acetyl-L-cysteine, a free radical scavenger. In addition, caspase inhibitors, zDEVD and zVAD, reduced apoptosis but not JNK and c-Jun phosphorylation induced by Cd, while overexpression of DN JNK1 inhibited caspase-3 activity. Taken together, our data suggested that the JNK/c-Jun signaling cascade plays a crucial role in Cd-induced neuronal cell apoptosis and provides a molecular linkage between oxidative stress and neuronal apoptosis.
Kim, Sun Don;
[1]
Biomedical Brain Research Center, National Institute of Health, Seoul 122-701 (Korea, Republic of)];
Moon, Chang Kyu;
[2]
Eun, Su-Yong;
[1]
College of Veterinary Medicine, Seoul National University, Seoul 122-701 (Korea, Republic of)];
Ryu, Pan Dong;
[3]
Jo, Sangmee Ahn
[4]
- Department of Biomedical Sciences, National Institute of Health, Seoul 122-701 (Korea, Republic of)
- College of Pharmacy, Seoul National University, Seoul 122-701 (Korea, Republic of)
- Biomedical Brain Research Center, National Institute of Health, Seoul 122-701 (Korea, Republic of)
- Department of Biomedical Sciences, National Institute of Health, Seoul 122-701 (Korea, Republic of) and College of Veterinary Medicine, Seoul National University, Seoul 122-701 (Korea, Republic of)
Citation Formats
Kim, Sun Don, Biomedical Brain Research Center, National Institute of Health, Seoul 122-701 (Korea, Republic of)], Moon, Chang Kyu, Eun, Su-Yong, College of Veterinary Medicine, Seoul National University, Seoul 122-701 (Korea, Republic of)], Ryu, Pan Dong, and Jo, Sangmee Ahn.
Identification of ASK1, MKK4, JNK, c-Jun, and caspase-3 as a signaling cascade involved in cadmium-induced neuronal cell apoptosis.
United States: N. p.,
2005.
Web.
doi:10.1016/j.bbrc.2004.11.173.
Kim, Sun Don, Biomedical Brain Research Center, National Institute of Health, Seoul 122-701 (Korea, Republic of)], Moon, Chang Kyu, Eun, Su-Yong, College of Veterinary Medicine, Seoul National University, Seoul 122-701 (Korea, Republic of)], Ryu, Pan Dong, & Jo, Sangmee Ahn.
Identification of ASK1, MKK4, JNK, c-Jun, and caspase-3 as a signaling cascade involved in cadmium-induced neuronal cell apoptosis.
United States.
https://doi.org/10.1016/j.bbrc.2004.11.173
Kim, Sun Don, Biomedical Brain Research Center, National Institute of Health, Seoul 122-701 (Korea, Republic of)], Moon, Chang Kyu, Eun, Su-Yong, College of Veterinary Medicine, Seoul National University, Seoul 122-701 (Korea, Republic of)], Ryu, Pan Dong, and Jo, Sangmee Ahn.
2005.
"Identification of ASK1, MKK4, JNK, c-Jun, and caspase-3 as a signaling cascade involved in cadmium-induced neuronal cell apoptosis."
United States.
https://doi.org/10.1016/j.bbrc.2004.11.173.
@misc{etde_20619404,
title = {Identification of ASK1, MKK4, JNK, c-Jun, and caspase-3 as a signaling cascade involved in cadmium-induced neuronal cell apoptosis}
author = {Kim, Sun Don, Biomedical Brain Research Center, National Institute of Health, Seoul 122-701 (Korea, Republic of)], Moon, Chang Kyu, Eun, Su-Yong, College of Veterinary Medicine, Seoul National University, Seoul 122-701 (Korea, Republic of)], Ryu, Pan Dong, and Jo, Sangmee Ahn}
abstractNote = {Cd induces oxidative stress and apoptosis in various cells by activating mitogen-activated protein kinases (MAPKs), but the precise signaling components of the MAPK cascade and their role in neuronal apoptosis are still unclear. Here, we report that Cd treatment of SH-SY5Y cells caused apoptosis through sequential phosphorylation of the apoptosis signal regulating kinase 1, MAPK kinase 4, c-Jun N-terminal kinase (JNK), and c-Jun as determined by overexpression of dominant negative (DN) constructs of these genes or using a specific JNK inhibitor SP600125. Both Cd-induced JNK and c-Jun phosphorylation and apoptosis were inhibited dramatically by N-acetyl-L-cysteine, a free radical scavenger. In addition, caspase inhibitors, zDEVD and zVAD, reduced apoptosis but not JNK and c-Jun phosphorylation induced by Cd, while overexpression of DN JNK1 inhibited caspase-3 activity. Taken together, our data suggested that the JNK/c-Jun signaling cascade plays a crucial role in Cd-induced neuronal cell apoptosis and provides a molecular linkage between oxidative stress and neuronal apoptosis.}
doi = {10.1016/j.bbrc.2004.11.173}
journal = []
issue = {1}
volume = {328}
journal type = {AC}
place = {United States}
year = {2005}
month = {Mar}
}
title = {Identification of ASK1, MKK4, JNK, c-Jun, and caspase-3 as a signaling cascade involved in cadmium-induced neuronal cell apoptosis}
author = {Kim, Sun Don, Biomedical Brain Research Center, National Institute of Health, Seoul 122-701 (Korea, Republic of)], Moon, Chang Kyu, Eun, Su-Yong, College of Veterinary Medicine, Seoul National University, Seoul 122-701 (Korea, Republic of)], Ryu, Pan Dong, and Jo, Sangmee Ahn}
abstractNote = {Cd induces oxidative stress and apoptosis in various cells by activating mitogen-activated protein kinases (MAPKs), but the precise signaling components of the MAPK cascade and their role in neuronal apoptosis are still unclear. Here, we report that Cd treatment of SH-SY5Y cells caused apoptosis through sequential phosphorylation of the apoptosis signal regulating kinase 1, MAPK kinase 4, c-Jun N-terminal kinase (JNK), and c-Jun as determined by overexpression of dominant negative (DN) constructs of these genes or using a specific JNK inhibitor SP600125. Both Cd-induced JNK and c-Jun phosphorylation and apoptosis were inhibited dramatically by N-acetyl-L-cysteine, a free radical scavenger. In addition, caspase inhibitors, zDEVD and zVAD, reduced apoptosis but not JNK and c-Jun phosphorylation induced by Cd, while overexpression of DN JNK1 inhibited caspase-3 activity. Taken together, our data suggested that the JNK/c-Jun signaling cascade plays a crucial role in Cd-induced neuronal cell apoptosis and provides a molecular linkage between oxidative stress and neuronal apoptosis.}
doi = {10.1016/j.bbrc.2004.11.173}
journal = []
issue = {1}
volume = {328}
journal type = {AC}
place = {United States}
year = {2005}
month = {Mar}
}