Leverrier Y, Thomas J, Perkins G R, Mangeney M, Collins M K, Marvel J
Immunologie cellulaire, LBMC de L'ENS Lyon CNRS UMR49 INRA LA 913, France.
Oncogene. 1997 Jan 30;14(4):425-30. doi: 10.1038/sj.onc.1200845.
The inhibition of cell death by growth factors plays a key role in the maintenance of the haematopoietic system homeostasis. However the mechanisms involved in this inhibition are still poorly understood. In order to determine if inhibition of apoptosis by growth factors is dependent only on the expression of survival genes, we have studied that process in the bone marrow derived IL-3 dependent cell line Baf-3. We show that, following IL-3 starvation, mRNA and protein levels of Bcl-X but not Bcl-2 decrease rapidly preceeding the onset of death. The death of IL-3 starved cells is asynchronous, starting between 6 to 8 h with 50% death being reached after 10 to 12 h. At any time point, apoptosis can be rapidly inhibited by growth factor re-addition. This has allowed us to determine that the inhibition of apoptosis by growth factor takes place at two levels. The first one, which we have called short term inhibition, is independent of mRNA and protein synthesis i.e. it takes place in the absence of survival gene neosynthesis and can be demonstrated during the first 6 h following growth factor re-addition. The second one corresponds to long-term survival-more than 24 h survival-and is strongly correlated with the induction of Bcl-X but not Bcl-2 gene expression. This induction of Bcl-X by IL-3 is shown to be dependent on MAP-kinase activation.
生长因子对细胞死亡的抑制作用在维持造血系统稳态中起着关键作用。然而，参与这种抑制作用的机制仍知之甚少。为了确定生长因子对细胞凋亡的抑制作用是否仅取决于存活基因的表达，我们在源自骨髓的依赖白细胞介素-3（IL-3）的细胞系Baf-3中研究了这一过程。我们发现，在IL-3饥饿后，Bcl-X而非Bcl-2的mRNA和蛋白质水平在死亡开始前迅速下降。IL-3饥饿细胞的死亡是异步的，在6至8小时之间开始，10至12小时后有50%的细胞死亡。在任何时间点，生长因子重新添加均可迅速抑制细胞凋亡。这使我们能够确定生长因子对细胞凋亡的抑制作用发生在两个层面。第一个层面，我们称之为短期抑制，它独立于mRNA和蛋白质合成，即在不存在存活基因新合成的情况下发生，并且可以在生长因子重新添加后的前6小时内得到证明。第二个层面对应长期存活——超过24小时的存活——并且与Bcl-X而非Bcl-2基因表达的诱导密切相关。IL-3对Bcl-X的这种诱导作用显示依赖于丝裂原活化蛋白激酶（MAP-激酶）的激活。
