ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract : The inhibitor of apoptosis (IAP) family of anti-apoptoticgenes, originally discovered in baculovirus, exists in animals ranging frominsects to humans. Here, we investigated the ability of IAPs to suppress celldeath in both a neuronal model of apoptosis and excitotoxicity. Cerebellargranule neurons undergo apoptosis when switched from 25 to 5 mMpotassium, and excitotoxic cell death in response to glutamate. We examinedthe endogenous expression of four members of the IAP family, Xchromosome-linked IAP (XIAP), rat IAP1 (RIAP1), RIAP2, and neuronal apoptosisinhibitory protein (NAIP), by semiquantitative reverse PCR and immunoblotanalysis in cultured cerebellar granule neurons. Cerebellar granule neuronsexpress significant levels of RIAP2 mRNA and protein, but expression of RIAP1,NAIP, and XIAP was not detected. RIAP2 mRNA content and protein levels did notchange when cells were switched from 25 to 5 mM potassium. Todetermine whether ectopic expression of IAP influenced neuronal survival afterpotassium withdrawal or glutamate exposure, we used recombinant adenoviralvectors to target XIAP, human IAP1 (HIAP1), HIAP2, and NAIP into cerebellargranule neurons. We demonstrate that forced expression of IAPs efficientlyblocked potassium withdrawal-inducedN-acetly-Asp-Glu-Val-Asp-specific caspase activity and reduced DNAfragmentation. However, neurons were only protected from apoptosis up to 24 hafter potassium withdrawal, not at later time points suggesting that IAPSdelay but do not block apoptosis in cerebellar granule neurons. In contrast,treatment with 100 μM or 1 mM glutamate did not induce caspase activity and adenoviral-mediated expression of IAPs had no influence on subsequent excitotoxic cell death.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.1999.0720292.x
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