RT Journal Article
SR Electronic
T1 An antisense oligodeoxynucleotide to glyceraldehyde-3-phosphate dehydrogenase blocks age-induced apoptosis of mature cerebrocortical neurons in culture.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 447
OP 454
VO 278
IS 1
A1 R Ishitani
A1 M Kimura
A1 K Sunaga
A1 N Katsube
A1 M Tanaka
A1 D M Chuang
YR 1996
UL http://jpet.aspetjournals.org/content/278/1/447.abstract
AB We recently reported that the age-induced apoptotic death of cultured cerebellar neurons is correlated with an increased expression of a particulate-bound 38-kDa protein that we identified as glyceraldehyde-3-phosphate dehydrogenase (GAPDH). To determine whether this phenomenon of GAPDH overexpression occurs in other cell types, we selected primary cultures of cerebrocortical cells for testing, because under normal culture conditions, cortical neurons die progressively after 15 days in vitro. As with cerebellar neurons, this age-induced neuronal death involves ultrastructural changes and internucleosomal DNA fragmentation characteristic of apoptosis and is effectively prevented by actinomycin-D and cycloheximide. Moreover, a GAPDH antisense oligodeoxyribonucleotide arrested this cortical neuronal death for about 4 to 5 days and thus was more effective than cycloheximide. By contrast, its corresponding sense oligonucleotide had no effect. Additionally, the age-induced apoptosis of cortical neuronal cultures is effectively protected by aurintricarboxylic acid and tetrahy-droaminoacridine (an antidementia drug). Before cell death, GAPDH mRNA levels increased by about 2-fold and the increase was blocked by the above-mentioned neuroprotective agents and the GAPDH antisense, but not sense, oligonucleotide. The effects of antisense oligonucleotide are more robust in the present case than those found with cerebellar neurons, and they indicate a significant, though at present not defined, role of GAPDH in the apoptotic process occurring in these two types of neurons.