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Ceramide induces neuronal apoptosis through mitogen-activated protein kinases and causes release of multiple mitochondrial proteins.
Mol Cell Neurosci 2005; 29(3):355-71MC

Abstract

Ceramide accumulates in neurons during various disorders associated with acute or chronic neurodegeneration. In these studies, we investigated the mechanisms of ceramide-induced apoptosis in primary cortical neurons using exogenous C(2) ceramide as well as inducing endogenous ceramide accumulation using inhibitors of glucosylceramide synthetase. Ceramide induced the translocation of certain, but not all, pro-apoptotic mitochondrial proteins: cytochrome c, Omi, SMAC, and AIF were released from the mitochondria, whereas Endonuclease G was not. Ceramide also selectively altered the phosphorylation state of members of the MAPK superfamily, causing dephosphorylation of ERK1/2 and hyperphosphorylation of p38 MAP kinases, but not affecting the phosphorylation of JNK or ERK5. Inhibitors of the p38 MAP kinase pathway (SB-202190 or SB-203580) and an inhibitor of the ERK1/2 pathway (U0126) reduced ceramide-induced neuronal death. These p38 and ERK1/2 inhibitors appear to block ceramide-activated apoptotic signaling upstream of the mitochondria, as they attenuated mitochondrial release of cytochrome c, Omi, AIF, and SMAC, as well as reducing ceramide-induced caspase-3 activation.

Authors+Show Affiliations

Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road, N.W., Research Building, Room EP-12, Washington, DC 20057, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15905098

Citation

Stoica, Bogdan A., et al. "Ceramide Induces Neuronal Apoptosis Through Mitogen-activated Protein Kinases and Causes Release of Multiple Mitochondrial Proteins." Molecular and Cellular Neurosciences, vol. 29, no. 3, 2005, pp. 355-71.
Stoica BA, Movsesyan VA, Knoblach SM, et al. Ceramide induces neuronal apoptosis through mitogen-activated protein kinases and causes release of multiple mitochondrial proteins. Mol Cell Neurosci. 2005;29(3):355-71.
Stoica, B. A., Movsesyan, V. A., Knoblach, S. M., & Faden, A. I. (2005). Ceramide induces neuronal apoptosis through mitogen-activated protein kinases and causes release of multiple mitochondrial proteins. Molecular and Cellular Neurosciences, 29(3), pp. 355-71.
Stoica BA, et al. Ceramide Induces Neuronal Apoptosis Through Mitogen-activated Protein Kinases and Causes Release of Multiple Mitochondrial Proteins. Mol Cell Neurosci. 2005;29(3):355-71. PubMed PMID: 15905098.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ceramide induces neuronal apoptosis through mitogen-activated protein kinases and causes release of multiple mitochondrial proteins. AU - Stoica,Bogdan A, AU - Movsesyan,Vilen A, AU - Knoblach,Susan M, AU - Faden,Alan I, PY - 2004/10/12/received PY - 2005/01/28/revised PY - 2005/02/16/accepted PY - 2005/5/21/pubmed PY - 2005/8/30/medline PY - 2005/5/21/entrez SP - 355 EP - 71 JF - Molecular and cellular neurosciences JO - Mol. Cell. Neurosci. VL - 29 IS - 3 N2 - Ceramide accumulates in neurons during various disorders associated with acute or chronic neurodegeneration. In these studies, we investigated the mechanisms of ceramide-induced apoptosis in primary cortical neurons using exogenous C(2) ceramide as well as inducing endogenous ceramide accumulation using inhibitors of glucosylceramide synthetase. Ceramide induced the translocation of certain, but not all, pro-apoptotic mitochondrial proteins: cytochrome c, Omi, SMAC, and AIF were released from the mitochondria, whereas Endonuclease G was not. Ceramide also selectively altered the phosphorylation state of members of the MAPK superfamily, causing dephosphorylation of ERK1/2 and hyperphosphorylation of p38 MAP kinases, but not affecting the phosphorylation of JNK or ERK5. Inhibitors of the p38 MAP kinase pathway (SB-202190 or SB-203580) and an inhibitor of the ERK1/2 pathway (U0126) reduced ceramide-induced neuronal death. These p38 and ERK1/2 inhibitors appear to block ceramide-activated apoptotic signaling upstream of the mitochondria, as they attenuated mitochondrial release of cytochrome c, Omi, AIF, and SMAC, as well as reducing ceramide-induced caspase-3 activation. SN - 1044-7431 UR - https://www.unboundmedicine.com/medline/citation/15905098/Ceramide_induces_neuronal_apoptosis_through_mitogen_activated_protein_kinases_and_causes_release_of_multiple_mitochondrial_proteins_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1044-7431(05)00031-X DB - PRIME DP - Unbound Medicine ER -