Nerve growth factor determines survival and death of PC12 cells by regulation of the bcl-x, bax, and caspase-3 genes

Rong, P; Bennie, AM; Epa, WR; Barrett, GL

Author(s): Rong, P; Bennie, AM; Epa, WR; Barrett, GL;
Details: Publication Year 1999-06,Volume 72,Issue #6,Page 2294-2300
Journal Title: JOURNAL OF NEUROCHEMISTRY
Publication Type: Journal Article
Abstract: We investigated the effects of nerve growth factor (NGF) and NGF withdrawal on expression of members of the bcl-2 family of genes and caspase-3 in PC12 cells. NGF regulated several members of the bcl-2 family and caspase-3 in a manner consistent with its 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 cells toward 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. Forced expression of bcl-xl after NGF withdrawal was sufficient to prevent cell death. Cell death was rapid when NGF was withdrawn after 5 days of treatment but relatively slow when NGF was withdrawn after only 1 or 2 days of treatment. 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.
Publisher: LIPPINCOTT WILLIAMS & WILKINS
Keywords: NEUROTROPHIN RECEPTOR; NEURONAL DEATH; DEFICIENT MICE; APOPTOSIS; FAMILY; P75; ACTIVATION; CED-4; DIFFERENTIATION; SPECIFICITIES
Publisher's Version: https://doi.org/10.1046/j.1471-4159.1999.0722294.x
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 1999-06-01 12:00:00