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Differential regulation of X-chromosome-linked inhibitor of apoptosis protein (XIAP) and caspase-3 by NMDA in developing hippocampal neurons; involvement of the mitochondrial pathway in NMDA-mediated neuronal survival.
Exp Cell Res. 2004 May 01; 295(2):290-9.EC

Abstract

N-methyl-d-aspartate (NMDA) subtype of glutamate receptors plays an important role during brain development and receptor activation has been shown to promote neuronal survival. The mechanisms by which NMDA increases neuronal survival are not fully understood. Here, we show that treatment with low concentrations of NMDA upregulates the neuroprotective molecule, X-chromosome-linked inhibitor of apoptosis protein (XIAP) in cultured hippocampal neurons at the post-transcriptional level. In contrast, NMDA treatment decreased mRNA and protein levels of caspase-3 in these neurons. The activation of the caspase-3 was also inhibited by NMDA, and the neurons were more resistant towards death caused by high concentrations of glutamate and staurosporine. Data on cytochrome c release in hippocampal neurons showed that NMDA pretreatment inhibits the mitochondrial pathway of cell death. The results demonstrate that the activation of NMDA receptors induces an anti-apoptotic program in hippocampal neurons that involves mitochondria and alterations of the levels of caspase-3 and XIAP. These findings are of importance for understanding the function of NMDA receptors in the control of neuronal survival during development and in other conditions.

Authors+Show Affiliations

Department of Neuroscience, Neurobiology, Biomedical Centre, Uppsala University, S-751 23 Uppsala, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15093730

Citation

Korhonen, Laura, et al. "Differential Regulation of X-chromosome-linked Inhibitor of Apoptosis Protein (XIAP) and Caspase-3 By NMDA in Developing Hippocampal Neurons; Involvement of the Mitochondrial Pathway in NMDA-mediated Neuronal Survival." Experimental Cell Research, vol. 295, no. 2, 2004, pp. 290-9.
Korhonen L, Näpänkangas U, Steen H, et al. Differential regulation of X-chromosome-linked inhibitor of apoptosis protein (XIAP) and caspase-3 by NMDA in developing hippocampal neurons; involvement of the mitochondrial pathway in NMDA-mediated neuronal survival. Exp Cell Res. 2004;295(2):290-9.
Korhonen, L., Näpänkangas, U., Steen, H., Chen, Y., Martinez, R., & Lindholm, D. (2004). Differential regulation of X-chromosome-linked inhibitor of apoptosis protein (XIAP) and caspase-3 by NMDA in developing hippocampal neurons; involvement of the mitochondrial pathway in NMDA-mediated neuronal survival. Experimental Cell Research, 295(2), 290-9.
Korhonen L, et al. Differential Regulation of X-chromosome-linked Inhibitor of Apoptosis Protein (XIAP) and Caspase-3 By NMDA in Developing Hippocampal Neurons; Involvement of the Mitochondrial Pathway in NMDA-mediated Neuronal Survival. Exp Cell Res. 2004 May 1;295(2):290-9. PubMed PMID: 15093730.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential regulation of X-chromosome-linked inhibitor of apoptosis protein (XIAP) and caspase-3 by NMDA in developing hippocampal neurons; involvement of the mitochondrial pathway in NMDA-mediated neuronal survival. AU - Korhonen,Laura, AU - Näpänkangas,Ulla, AU - Steen,Håkan, AU - Chen,Yuming, AU - Martinez,Rodrigo, AU - Lindholm,Dan, PY - 2003/08/19/received PY - 2003/11/26/revised PY - 2004/4/20/pubmed PY - 2004/5/21/medline PY - 2004/4/20/entrez SP - 290 EP - 9 JF - Experimental cell research JO - Exp Cell Res VL - 295 IS - 2 N2 - N-methyl-d-aspartate (NMDA) subtype of glutamate receptors plays an important role during brain development and receptor activation has been shown to promote neuronal survival. The mechanisms by which NMDA increases neuronal survival are not fully understood. Here, we show that treatment with low concentrations of NMDA upregulates the neuroprotective molecule, X-chromosome-linked inhibitor of apoptosis protein (XIAP) in cultured hippocampal neurons at the post-transcriptional level. In contrast, NMDA treatment decreased mRNA and protein levels of caspase-3 in these neurons. The activation of the caspase-3 was also inhibited by NMDA, and the neurons were more resistant towards death caused by high concentrations of glutamate and staurosporine. Data on cytochrome c release in hippocampal neurons showed that NMDA pretreatment inhibits the mitochondrial pathway of cell death. The results demonstrate that the activation of NMDA receptors induces an anti-apoptotic program in hippocampal neurons that involves mitochondria and alterations of the levels of caspase-3 and XIAP. These findings are of importance for understanding the function of NMDA receptors in the control of neuronal survival during development and in other conditions. SN - 0014-4827 UR - https://www.unboundmedicine.com/medline/citation/15093730/Differential_regulation_of_X_chromosome_linked_inhibitor_of_apoptosis_protein__XIAP__and_caspase_3_by_NMDA_in_developing_hippocampal_neurons L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014482703006797 DB - PRIME DP - Unbound Medicine ER -