Premium
Nerve Growth Factor Determines Survival and Death of PC12 Cells by Regulation of the bcl‐x, bax , and caspase‐3 Genes
Author(s) -
Rong Pei,
Bennie Antoinette M.,
Epa W. Ruwan,
Barrett Graham L.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0722294.x
Subject(s) - nerve growth factor , apoptosis , bcl xl , programmed cell death , caspase , microbiology and biotechnology , caspase 3 , biology , signal transduction , caspase 9 , medicine , endocrinology , receptor , genetics
We investigated the effects of nerve growth factor (NGF)and NGF withdrawal on expression of members of the bcl‐2 family ofgenes and caspase‐3 in PC12 cells. NGF regulated several members ofthe bcl‐2 family and caspase‐3 in a manner consistent withits effect on apoptosis in PC12 cells. Levels of bcl‐xl, bcl‐xs , and caspase‐3 mRNAs were increased by NGF treatment. The increases in caspase‐3 and bcl‐xs levels should have disposed the cellstoward apoptosis but were opposed by the simultaneous increase in bcl‐xl level. NGF withdrawal resulted in abrupt down‐regulation of bcl‐xl and up‐regulation of bax , favoring apoptosis. Forcedexpression of bcl‐xl after NGF withdrawal was sufficient to preventcell death. Cell death was rapid when NGF was withdrawn after 5 days oftreatment but relatively slow when NGF was withdrawn after only 1 or 2 days oftreatment. This was consistent with the reduced accumulation of caspase‐3 mRNA with shorter NGF treatments. These results indicate that Bcl‐xl, Bcl‐xs, Bax, and caspase‐3 are important regulators of apoptosis in PC12 cells. Furthermore, regulation of their mRNA levels is implicated in the signal transduction of NGF.