Tags

Type your tag names separated by a space and hit enter

The role of p38 MAPK and JNK in Arsenic trioxide-induced mitochondrial cell death in human cervical cancer cells.
J Cell Physiol. 2008 Oct; 217(1):23-33.JC

Abstract

Previously, we have shown that the release of AIF from mitochondria is required for As2O3-induced cell death in human cervical cancer cells, and that reactive oxygen species (ROS) is necessary for AIF release from mitochondria. In this study, we further investigated the role of MAPKs in ROS-mediated mitochondrial apoptotic cell death triggered by As2O3. As2O3-induced apoptotic cell death in HeLa cells was associated with activation and mitochondrial translocation of Bax, a marked phosphorylation of Bcl-2, reduction of Bcl-2 and Bax interaction, dissipation of mitochondrial membrane potential. Using small interfering RNA, reduced Bax expression effectively attenuated As2O3-induced mitochondrial membrane potential loss and apoptotic cell death. Moreover, the phosphorylation of Bcl-2 induced by As2O3 diminished its ability to bind to Bax. Treatment of cells with As2O3 activated both the p38 MAPK and JNK pathways. Mitochondrial translocation of Bax was completely suppressed in the presence of p38 MAPK inhibitor PD169316 or si-p38 MAPK. The As2O3-induced Bcl-2 phosphorylation was attenuated largely by JNK inhibition using SP600125 or si-JNK and to some extent by p38 MAPK inhibition with PD169316 or si-p38 MAPK. In addition, N-acetyl-L-cystein (NAC), a thiol-containing anti-oxidant, completely blocked As2O3-induced p38 MAPK and JNK activations, mitochondria translocation of Bax, and phosphorylation of Bcl-2. These results support a notion that ROS-mediated activations of p38 MAPK and JNK in response to As2O3 treatment signals activation of Bax and phosphorylation of Bcl-2, resulting in mitochondrial apoptotic cell death in human cervical cancer cells.

Authors+Show Affiliations

Laboratory of Molecular Biochemistry, Department of Chemistry, Hanyang University, Seoul, South Korea.No affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18412143

Citation

Kang, Young-Hee, and Su-Jae Lee. "The Role of P38 MAPK and JNK in Arsenic Trioxide-induced Mitochondrial Cell Death in Human Cervical Cancer Cells." Journal of Cellular Physiology, vol. 217, no. 1, 2008, pp. 23-33.
Kang YH, Lee SJ. The role of p38 MAPK and JNK in Arsenic trioxide-induced mitochondrial cell death in human cervical cancer cells. J Cell Physiol. 2008;217(1):23-33.
Kang, Y. H., & Lee, S. J. (2008). The role of p38 MAPK and JNK in Arsenic trioxide-induced mitochondrial cell death in human cervical cancer cells. Journal of Cellular Physiology, 217(1), 23-33. https://doi.org/10.1002/jcp.21470
Kang YH, Lee SJ. The Role of P38 MAPK and JNK in Arsenic Trioxide-induced Mitochondrial Cell Death in Human Cervical Cancer Cells. J Cell Physiol. 2008;217(1):23-33. PubMed PMID: 18412143.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of p38 MAPK and JNK in Arsenic trioxide-induced mitochondrial cell death in human cervical cancer cells. AU - Kang,Young-Hee, AU - Lee,Su-Jae, PY - 2008/4/17/pubmed PY - 2008/8/20/medline PY - 2008/4/17/entrez SP - 23 EP - 33 JF - Journal of cellular physiology JO - J Cell Physiol VL - 217 IS - 1 N2 - Previously, we have shown that the release of AIF from mitochondria is required for As2O3-induced cell death in human cervical cancer cells, and that reactive oxygen species (ROS) is necessary for AIF release from mitochondria. In this study, we further investigated the role of MAPKs in ROS-mediated mitochondrial apoptotic cell death triggered by As2O3. As2O3-induced apoptotic cell death in HeLa cells was associated with activation and mitochondrial translocation of Bax, a marked phosphorylation of Bcl-2, reduction of Bcl-2 and Bax interaction, dissipation of mitochondrial membrane potential. Using small interfering RNA, reduced Bax expression effectively attenuated As2O3-induced mitochondrial membrane potential loss and apoptotic cell death. Moreover, the phosphorylation of Bcl-2 induced by As2O3 diminished its ability to bind to Bax. Treatment of cells with As2O3 activated both the p38 MAPK and JNK pathways. Mitochondrial translocation of Bax was completely suppressed in the presence of p38 MAPK inhibitor PD169316 or si-p38 MAPK. The As2O3-induced Bcl-2 phosphorylation was attenuated largely by JNK inhibition using SP600125 or si-JNK and to some extent by p38 MAPK inhibition with PD169316 or si-p38 MAPK. In addition, N-acetyl-L-cystein (NAC), a thiol-containing anti-oxidant, completely blocked As2O3-induced p38 MAPK and JNK activations, mitochondria translocation of Bax, and phosphorylation of Bcl-2. These results support a notion that ROS-mediated activations of p38 MAPK and JNK in response to As2O3 treatment signals activation of Bax and phosphorylation of Bcl-2, resulting in mitochondrial apoptotic cell death in human cervical cancer cells. SN - 1097-4652 UR - https://www.unboundmedicine.com/medline/citation/18412143/The_role_of_p38_MAPK_and_JNK_in_Arsenic_trioxide_induced_mitochondrial_cell_death_in_human_cervical_cancer_cells_ DB - PRIME DP - Unbound Medicine ER -