Copani A, Bruno V, Dell'Albani P, Battaglia G, Barresi V, Caruso A, Nicoletti F, Condorelli D F
Institute of Pharmacology, School of Medicine, University of Catania, Italy.
Neurochem Res. 1995 May;20(5):611-6. doi: 10.1007/BF01694544.
Cultured cerebellar granule cells underwent apoptotic degeneration when grown in medium containing 10 instead of 25 mM K+. Knowing that apoptosis is associated with changes in the expression of primary response genes, we have measured c-fos, zif/268, and c-jun mRNA levels during maturation of cultured granule cells grown in 10 or 25 mM K+. The constitutive expression of c-fos and zif/268 was differentially regulated by extracellular K+ concentration at 5 days of maturation in vitro (DIV), when cells grown under suboptimal conditions (i.e. in 10 mM K+) are committed to degenerate. At this stage, c-fos mRNA levels were detectable only in cultures grown in 25 mM K+, whereas zif/268 mRNA levels were dramatically elevated in cultures grown in 10 mM K+. This provides one of the few conditions in which c-fos and zif/268 are differentially regulated in nerve cells. Substantial changes in c-jun, or beta-actin mRNA levels were detectable only at 7 DIV, when the percentage of apoptotic cells had already reached a plateau in cultures grown in 10 mM K+. We speculate that changes in the expression of zif/268 are important in the gene program associated with the induction of apoptosis by trophic deprivation in cultured neurons.
当培养的小脑颗粒细胞在含有10 mM而非25 mM钾离子的培养基中生长时，会发生凋亡性退变。鉴于凋亡与初级反应基因表达的变化相关，我们测定了在10 mM或25 mM钾离子中生长的培养颗粒细胞成熟过程中c-fos、zif/268和c-jun的mRNA水平。在体外成熟5天（DIV）时，c-fos和zif/268的组成型表达受到细胞外钾离子浓度的差异调节，此时在次优条件下（即在10 mM钾离子中）生长的细胞开始退变。在此阶段，c-fos mRNA水平仅在25 mM钾离子培养的细胞中可检测到，而zif/268 mRNA水平在10 mM钾离子培养的细胞中显著升高。这提供了少数几个神经细胞中c-fos和zif/268受到差异调节的条件之一。只有在7 DIV时，当在10 mM钾离子培养的细胞中凋亡细胞百分比已达到平台期时，才可检测到c-jun或β-肌动蛋白mRNA水平的显著变化。我们推测，zif/268表达的变化在与培养神经元中营养剥夺诱导凋亡相关的基因程序中很重要。
