Interactions between Bcl-2 and the IGF system control apoptosis in the developing mouse brain

被引:36
作者
Baker, NL
Russo, VC
Bernard, O
D'Ercole, AJ
Werther, GA
机构
[1] Royal Childrens Hosp, Ctr Hormone Res, Parkville, Vic 3052, Australia
[2] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
[3] Univ N Carolina, Dept Pediat, Div Endocrinol, Chapel Hill, NC 27599 USA
来源
DEVELOPMENTAL BRAIN RESEARCH | 1999年 / 118卷 / 1-2期
关键词
Bcl-2; IGF-I; IGFBP-2; apoptosis; neuronal cell death; transgenic mouse;
D O I
10.1016/S0165-3806(99)00136-4
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The IGF system and the pro-survival Bcl-2 proteins protect cells from apoptosis and play a key role in brain development. In order to examine a possible relationship between these two potent anti-apoptotic systems, we utilised two transgenic mice models overexpressing either Bcl-2 or IGF-I proteins in olfactory bulb (OB) or cerebellar neurons, respectively. We have demonstrated that while the organization of the defined layers of the OB from the bcl-2 transgenic and wildtype mice cultured in serum free medium (SF) was similarly poor, the mitral cell layer from the transgenic mice was expanded and their neurons were well preserved. Addition of IGF-I improved the definition of the layers normally present within the OB, in both wildtype and bcl-2 transgenic mice, and restored wildtype mitral cell layer structure and neuronal survival similar to that in bcl-2 mice, whose mitral cell survival was not further enhanced by IGF-I. Immunoreactivity for IGF-I and IGFBP-2 was markedly increased in these Bcl-2-expressing mitral cells compared to wildtype mice. In newborn IGF-I transgenic mice, cerebellar Purkinje cells overexpressing IGF-I showed markedly increased immunoreactivity for Bcl-2 and IGFBP-2, These studies indicate that in the developing brain IGF-I modulates expression of its major binding protein IGFBP-2, as well as the Bcl-2 protein. In addition apoptosis caused by culturing OBs in SF medium, is inhibited by expression of Bcl-2 in the mitral neurons and is associated with enhanced expression of the IGF system, including IGF-I and IGFBP-2. The later may thus play a role in IGF targeting. This complex interaction between the two potent anti-apoptotic systems is likely to provide a robust system of cell protection during brain development and repair. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:109 / 118
页数:10
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