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p38 Mitogen-activated protein kinase regulates Bax translocation in cyanide-induced apoptosis.
Toxicol Sci. 2003 Sep; 75(1):99-107.TS

Abstract

Execution of cyanide-induced apoptosis is mediated by release of cytochrome c from mitochondria. To determine how cyanide initiates cytochrome c release, Bax translocation was investigated in primary cultures of cortical neurons. Under nonapoptotic (control) conditions, Bax resided predominantly in the cytoplasm. After 300-microM cyanide treatment for 1 h, Bax translocated to the mitochondria, as shown by immunocytochemical staining and subcellular fractionation; Western blot analysis confirmed "cytosol-to-mitochondria" translocation of Bax. Temporal analysis showed that Bax translocation preceded cytochrome c release from the mitochondria, which was initiated 3 h after cyanide treatment. In double-immunofluorescence labeling for both Bax and cytochrome c, it was observed that cytochrome c was released only in cells showing Bax in mitochondria. The role of p38 mitogen-activated protein (MAP) kinase in Bax translocation was studied. The p38 MAP kinase was activated 30 min after cyanide, and its phosphorylation level of activity began to decrease 3 h later. SB203580, a p38 MAP kinase inhibitor, blocked translocation of Bax to mitochondria, whereas SB202474, a control peptide, had no effect on translocation. Inhibition of p38 MAP kinase by SB203580 blocked all downstream effects of Bax translocation, including cytochrome c release, caspase activation, and internucleosomal DNA fragmentation. These results demonstrated that Bax translocation is critical for cyanide-induced cytochrome c release and that p38 MAP kinase regulates Bax translocation from cytosol to mitochondria.

Authors+Show Affiliations

Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907-1333, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12805646

Citation

Shou, Y, et al. "P38 Mitogen-activated Protein Kinase Regulates Bax Translocation in Cyanide-induced Apoptosis." Toxicological Sciences : an Official Journal of the Society of Toxicology, vol. 75, no. 1, 2003, pp. 99-107.
Shou Y, Li L, Prabhakaran K, et al. P38 Mitogen-activated protein kinase regulates Bax translocation in cyanide-induced apoptosis. Toxicol Sci. 2003;75(1):99-107.
Shou, Y., Li, L., Prabhakaran, K., Borowitz, J. L., & Isom, G. E. (2003). P38 Mitogen-activated protein kinase regulates Bax translocation in cyanide-induced apoptosis. Toxicological Sciences : an Official Journal of the Society of Toxicology, 75(1), 99-107.
Shou Y, et al. P38 Mitogen-activated Protein Kinase Regulates Bax Translocation in Cyanide-induced Apoptosis. Toxicol Sci. 2003;75(1):99-107. PubMed PMID: 12805646.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - p38 Mitogen-activated protein kinase regulates Bax translocation in cyanide-induced apoptosis. AU - Shou,Y, AU - Li,L, AU - Prabhakaran,K, AU - Borowitz,J L, AU - Isom,G E, Y1 - 2003/06/12/ PY - 2003/6/14/pubmed PY - 2004/8/3/medline PY - 2003/6/14/entrez SP - 99 EP - 107 JF - Toxicological sciences : an official journal of the Society of Toxicology JO - Toxicol Sci VL - 75 IS - 1 N2 - Execution of cyanide-induced apoptosis is mediated by release of cytochrome c from mitochondria. To determine how cyanide initiates cytochrome c release, Bax translocation was investigated in primary cultures of cortical neurons. Under nonapoptotic (control) conditions, Bax resided predominantly in the cytoplasm. After 300-microM cyanide treatment for 1 h, Bax translocated to the mitochondria, as shown by immunocytochemical staining and subcellular fractionation; Western blot analysis confirmed "cytosol-to-mitochondria" translocation of Bax. Temporal analysis showed that Bax translocation preceded cytochrome c release from the mitochondria, which was initiated 3 h after cyanide treatment. In double-immunofluorescence labeling for both Bax and cytochrome c, it was observed that cytochrome c was released only in cells showing Bax in mitochondria. The role of p38 mitogen-activated protein (MAP) kinase in Bax translocation was studied. The p38 MAP kinase was activated 30 min after cyanide, and its phosphorylation level of activity began to decrease 3 h later. SB203580, a p38 MAP kinase inhibitor, blocked translocation of Bax to mitochondria, whereas SB202474, a control peptide, had no effect on translocation. Inhibition of p38 MAP kinase by SB203580 blocked all downstream effects of Bax translocation, including cytochrome c release, caspase activation, and internucleosomal DNA fragmentation. These results demonstrated that Bax translocation is critical for cyanide-induced cytochrome c release and that p38 MAP kinase regulates Bax translocation from cytosol to mitochondria. SN - 1096-6080 UR - https://www.unboundmedicine.com/medline/citation/12805646/p38_Mitogen_activated_protein_kinase_regulates_Bax_translocation_in_cyanide_induced_apoptosis_ L2 - https://academic.oup.com/toxsci/article-lookup/doi/10.1093/toxsci/kfg157 DB - PRIME DP - Unbound Medicine ER -