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| Evidence that glyceraldehyde-3-phosphate dehydrogenase is involved in age-induced apoptosis in mature cerebellar neurons in culture |
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| Author(s): Ishitani R, Sunaga K, Hirano A, Saunders P, Katsube N, Chuang DM |
| Source: JOURNAL OF NEUROCHEMISTRY Volume: 66 Issue: 3 Pages: 928-935 Published: MAR 1996 |
| Times Cited: 132 References: 43 |
| Abstract: Under typical culture conditions, cerebellar granule cells die abruptly after 17 days in vitro. This burst of neuronal death involves ultrastructural changes and internucleosomal DNA fragmentations characteristic of apoptosis and is effectively arrested by pretreatment with actinomycin-D and cycloheximide. The level of a 38-kDa protein in the particulate fraction is markedly increased during age-induced cell death and by pretreatment with NMDA, which potentiates this cell death. Conversely, the age-induced increment of the 38-kDa particulate protein is suppressed by actinomycin-D and cycloheximide. N-terminal microsequencing of the 38-kDa protein revealed sequence identity with glyceraldehyde-3-phosphate dehydrogenase (GAPDH). A GAPDH antisense oligodeoxyribonucleotide blocks age-induced expression of the particulate 38-kDa protein and effectively inhibits neuronal apoptosis. In contrast, the corresponding sense oligonucleotide of GAPDH was completely ineffective in preventing the age-induced neuronal death and the 38-kDa protein overexpression. Moreover, the age-induced expression of the 38-kDa protein is preceded by a pronounced increase in the GAPDH mRNA level, which is abolished by actinomycin-D, cycloheximide, or the GAPDH antisense, but not sense, oligonucleotide, Thus, our results suggest that overexpression of GAPDH in the particulate fraction has a direct role in age-induced apoptosis of cerebellar neurons. |
| Document Type: Article |
| Language: English |
| Reprint Address: Ishitani, R (reprint author), JOSAI UNIV, GRP CELLULAR NEUROBIOL, SAKADO, SAITAMA 35002 JAPAN |
Addresses:
1. ONO PHARMACEUT CO LTD, MINASE RES INST, OSAKA, JAPAN
2. NIMH, BIOL PSYCHIAT BRANCH, MOLEC NEUROBIOL SECT, BETHESDA, MD 20892 USA |
| Publisher: LIPPINCOTT-RAVEN PUBL, 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 |
| Subject Category: Biochemistry & Molecular Biology; Neurosciences |
| IDS Number: TV786 |
| ISSN: 0022-3042 |
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