Expression of apoptosis inhibitor protein Mcl1 linked to neuroprotection in CNS neurons

Expression of apoptosis inhibitor protein Mcl1 linked to neuroprotection in CNS neurons

Author Mori, M. Google Scholar
Burgess, D. L. Google Scholar
Gefrides, L. A. Google Scholar
Foreman, P. J. Google Scholar
Opferman, J. T. Google Scholar
Korsmeyer, S. J. Google Scholar
Cavalheiro, Esper Abrão Autor UNIFESP Google Scholar
Naffah-Mazzacoratti, Maria da Graca Autor UNIFESP Google Scholar
Noebels, J. L. Google Scholar
Institution Baylor Coll Med
Harvard Univ
Universidade Federal de São Paulo (UNIFESP)
Abstract Mcl1 is a Bcl2-related antiapoptotic protein originally isolated from human myeloid leukemia cells. Unlike Bcl2, expression has not been reported in CNS neurons. We isolated Mcl1 in a direct screen for candidate modifier genes of neuronal vulnerability by differential display of mRNAs upregulated following prolonged seizures in two mouse strains with contrasting levels of hippocampal cell death. Mcl1 is widely expressed in neurons, and transcription is rapidly induced in both strains. in resistant C57Bl/6J mice, Mcl1 protein levels remain persistently elevated in hippocampal pyramidal neurons after seizures, but fall rapidly in C3H/HeJ hippocampus, coinciding with extensive neuronal apoptosis. DNA damage and caspase-mediated cell death were strikingly increased in Mcl1-deficient mice when compared to +/+ littermates after similar seizures. We identify Mcl1 as a neuronal gene responsive to excitotoxic insult in the brain, and link relative levels of Mcl1 expression to inherited differences in neuronal thresholds for apoptosis.
Keywords Mcl1
neuronal cell death
modifier genes
Language English
Date 2004-11-01
Published in Cell Death and Differentiation. London: Nature Publishing Group, v. 11, n. 11, p. 1223-1233, 2004.
ISSN 1350-9047 (Sherpa/Romeo, impact factor)
Publisher Nature Publishing Group
Extent 1223-1233
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000224465700009

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