Hamnér S, Skoglösa Y, Lindholm D
Department of Neuroscience, Developmental Neuroscience, Uppsala, Sweden.
Neuroscience. 1999;91(2):673-84. doi: 10.1016/s0306-4522(98)00642-3.
The bcl-2 family of proteins comprises both anti-apoptotic and pro-apoptotic members, which play a pivotal role in regulating cell death. Bcl-w is a recently identified member of this family, which was shown to inhibit apoptosis in haemopoietic cell lines. However, the function and expression patterns of bcl-w in the nervous system have so far not been described. We have cloned complementary DNA corresponding to rat bcl-w and analysed the expression of bcl-w messenger RNA during rat brain development, using RNA blotting and in situ hybridization techniques. We also compared the expression patterns of bcl-w with those of bcl-xL. During brain development, the levels of bcl-w messenger RNA were found to increase, with highest expression located to specific regions of the mature brain, such as hippocampus, cerebellum, piriform cortex and locus coeruleus. Bcl-w messenger RNA was expressed by neurons, as shown with double labeling with neuronal markers. In contrast to bcl-w, bcl-xL messenger RNA expression levels were highest during early development, particularly in cortex, hippocampus, thalamus, spinal cord and dorsal root ganglia. During postnatal development the expression of bcl-xL messenger RNA decreased and were only detected at low levels in the adult nervous system. As shown earlier for bcl-2, the expression of bcl-w and bcl-x messenger RNA in cultured cerebellar granule cells was not altered by the deprivation of neurotrophic factors. The present results suggest that bcl-w may play an important role in the mature nervous system.
bcl-2蛋白家族包括抗凋亡和促凋亡成员,它们在调节细胞死亡中起关键作用。Bcl-w是该家族最近鉴定出的成员,已证明其可抑制造血细胞系中的细胞凋亡。然而,迄今为止,尚未描述bcl-w在神经系统中的功能和表达模式。我们克隆了与大鼠bcl-w对应的互补DNA,并使用RNA印迹和原位杂交技术分析了大鼠脑发育过程中bcl-w信使RNA的表达。我们还比较了bcl-w与bcl-xL的表达模式。在脑发育过程中,发现bcl-w信使RNA的水平升高,其最高表达位于成熟脑的特定区域,如海马体、小脑、梨状皮质和蓝斑。如用神经元标记物双重标记所示,bcl-w信使RNA由神经元表达。与bcl-w相反,bcl-xL信使RNA的表达水平在早期发育期间最高,特别是在皮质、海马体、丘脑、脊髓和背根神经节中。在出生后发育过程中,bcl-xL信使RNA的表达下降,在成年神经系统中仅以低水平检测到。如先前对bcl-2的研究所示,培养的小脑颗粒细胞中bcl-w和bcl-x信使RNA的表达不受神经营养因子剥夺的影响。目前的结果表明,bcl-w可能在成熟神经系统中起重要作用。