The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Inhibition of Akt Kinase by Cell-permeable Ceramide and Its Implications for Ceramide-induced Apoptosis
Open accessAbstract
Ceramide is an important lipid messenger involved in mediating a variety of cell functions including apoptosis. However, mechanisms responsible for ceramide-induced apoptosis remain unclear. We investigated the possibility that ceramide may decrease antiapoptotic signaling in cells by inhibiting Akt kinase activity. Our data show that C2-ceramide induces apoptosis in HMN1 motor neuron cells and decreases both basal and insulin- or serum-stimulated Akt kinase activity 65-70%. These results are consistent with decreased Akt kinase activity being involved in the apoptotic effects of ceramide. This possibility is further supported by studies showing that constitutively active Akt kinase decreases C2-ceramide-induced death of HMN1 cells as well as COS-7 cells. Decreased Akt activity is not due to ceramide activating the ceramide-activated protein phosphatase or to a direct inhibition of Akt kinase by ceramide, suggesting that ceramide acts upstream of Akt kinase to decrease its activity. Treating cells with C2-ceramide does not affect phosphorylation of insulin receptor substrate-1, interactions between insulin receptor substrate-1 and p85, or insulin-stimulated phosphatidylinositol 3-kinase activity, suggesting that the effects of C2-ceramide on Akt kinase are not mediated through modulating phosphatidylinositol 3-kinase. In sum, our results suggest that inhibition of the key antiapoptotic kinase, Akt, may play an important role in ceramide-induced apoptosis.
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Cites
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Self-citationProgrammed Cell Death Induced by Ceramide
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Neurotrophins: Roles in Neuronal Development and Function
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Principles of bioactive lipid signalling: lessons from sphingolipids
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Mechanisms of Insulin Action and Insulin Resistance
Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028
Trk Receptors: Roles in Neuronal Signal Transduction
Huang, E. J., & Reichardt, L. F. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161629 · Cited by 2,537
Metadata
- Authors
- Zhou, H., Summers, S. A., Birnbaum, M. J., & Pittman, R. N.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1998-06
- Volume
- 273
- Issue
- 26
- Pages
- 16568-16575
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2047287528
- Cited by
- 347
- References
- 45
- FWCI
- 10.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Zhou, H., Summers, S. A., Birnbaum, M. J., & Pittman, R. N. (1998). Inhibition of Akt Kinase by Cell-permeable Ceramide and Its Implications for Ceramide-induced Apoptosis. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.273.26.16568
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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