TIS GENE-EXPRESSION IN CULTURED RAT ASTROCYTES - MULTIPLE PATHWAYS OF INDUCTION BY MITOGENS
TIS GENE-EXPRESSION IN CULTURED RAT ASTROCYTES - MULTIPLE PATHWAYS OF INDUCTION BY MITOGENS
复制标题
DOI：
10.1002/jnr.490230303
复制
发表时间：
1989-07-01
影响因子：
4.2
通讯作者：
HERSCHMAN, HR
中科院分区：
文献类型：
--
作者：
ARENANDER, AT;LIM, RW;HERSCHMAN, HR
大鼠新皮质星形胶质细胞继代培养物中 TIS1 和 TIS11（Lim 等人：Oncogene 1:263-270, 1987）对十四烷酰佛波醇乙酸酯 (TPA) 的反应比对表皮生长因子 (EGF) 或成纤维细胞生长因子 (FGF) 的反应要高得多。相比之下，EGF、FGF 和 TPA 在诱导 TIS8 和 TIS28/c-fos mRNA 积累方面同样有效。这些数据表明TPA和多肽有丝分裂原可能通过不同的途径诱导TIS基因表达。当最大诱导浓度的 EGF 和 FGF 共同施用到星形胶质细胞培养物中时，TIS mRNA 积累并不高于单个生长因子观察到的积累，表明 EGF 和 FGF 饱和了其诱导途径中的一个共同的限制步骤。相反，当将EGF或FGF与最大诱导水平的TPA结合呈递给星形胶质细胞时，所产生的TIS mRNA积累水平至少与单个有丝分裂原诱导的水平总和一样高。 [3H]-胸苷掺入的刺激表现出相同的相互作用模式； EGF和FGF共同施用并不比单独使用任一多肽有丝分裂原更有效，但是，当与最大诱导浓度的TPA一起呈递于星形胶质细胞培养物时，EGF或FGF能够增加[3H]-胸苷的掺入。如果 TRPA 暴露期间存在放线菌酮 (CHX)，则会发生所有 TIS 基因的超诱导。各种 TIS 基因再次出现两种不同类型的反应： TIS1、TIS7、TIS11 和 TIS28/c-fos mRNA 积累的超诱导范围为 10 至 20 倍，而 TIS8 和 TIS10 的 CHX 超诱导则要温和得多，范围为 2 至 3 倍。当星形胶质细胞在外周活性苯二氮卓类 (BZD) Ro5-4864 存在的情况下用 TPA 攻击时，也会发生 TIS 基因表达的差异超诱导，范围从五倍高 (TIS28/c-fos) 到无超诱导效应 (TIS8)。 BZD 和 CHX 超诱导各种 TIS 基因的时间模式和相对功效非常不同。 TIS 基因积累的诱导是通过几个独立的途径响应多种配体而发生的，并且可以通过许多其他因素进行二次调节。这组瞬时初级反应基因产物的差异表达可能在整合影响细胞的信息和指导其生理反应方面发挥重要作用。
Accumulation of TIS1 and TIS11 (Lim et al.: Oncogene 1:263-270, 1987) mRNAs in secondary cultures of rat neocortical astrocytes was much greater in response to tetradecanoyl phorbol acetate (TPA) than in response to either epidermal growth factor (EGF) or fibroblast growth factor (FGF). In contrast, EGF, FGF, and TPA were equally effective in inducing accumulation of TIS8 and TIS28/c-fos mRNAs. These data suggested that TPA and the polypeptide mitogens might induce TIS gene expression by distinct pathways. When maximally inducing concentrations of EGF and FGF were co-administered to astrocytes cultures, TIS mRNA accumulations were no greater that those observed for the individual growth factors, suggesting that EGF and FGF saturate a common, limiting step in their induction pathways. In contrast, when either EGF or FGF was presented to astrocytes in combination with maximally inducing levels of TPA, the resulting levels of accumulation of TIS mRNAs were at least as great as the sum of the levels induced by the individual mitogens. Stimulation of [3H]-thymidine incorporation demonstrated an identical pattern of interact; EGF and FGF co-adminstration was no more effective than either polypeptide mitogen alone, but, when presented to astrocyte cultures along with maximally inducing concentrations of TPA, either EGF or FGF was able to increase incorporation of [3H]-thymidine. Superinduction of all the TIS genes occurred if cycloheximide (CHX) was present during TRPA exposure. Once again, two distinct classes of responses of the various TIS genes occurred; superinduction of TIS1, TIS7, TIS11, and TIS28/c-fos mRNA accumulation ranged from 10- to 20-fold, while CHX superinduction of TIS8 and TIS10 was far more modest, ranging from 2- to 3-fold. Differential superinduction of TIS gene expression also occurred when astrocytes were challenged with TPA in the presence of the peripherally active benzodiazepine (BZD) Ro5-4864, ranging form a high of fivefold (TIS28/c-fos) to no superinduction effect (TIS8). The temporal patterns and relative efficacies of BZD and CHX superinduction of the various TIS genes were quite distinct. Induction of TIS gene accumulation occurs in response to a wide variety ligands by several independent pathways and can be secondarily modulated by a number of additional factors. The differential expression of this set of transient primary-response gene products may play a major role in integrating information that impinges on cells and in directing their physiological responses.