Malam-Souley R, Campan M, Gadeau A P, Desgranges C
Unité 8 de Cardiologie, Institut National de la Santé et de la Recherche Médicale, Pessac, France.
Am J Physiol. 1993 Apr;264(4 Pt 1):C783-8. doi: 10.1152/ajpcell.1993.264.4.C783.
Because exogenous ATP is suspected to influence the proliferative process, its effects on the cell cycle progression of arterial smooth muscle cells were studied by investigating changes in the mRNA steady-state level of cell cycle-dependent genes. Stimulation of cultured quiescent smooth muscle cells by exogenous ATP induced chronological activation not only of immediate-early but also of delayed-early cell cycle-dependent genes, which were usually expressed after a mitogenic stimulation. In contrast, ATP did not increase late G1 gene mRNA level, demonstrating that this nucleotide induces a limited cell cycle progression of arterial smooth muscle cells through the G1 phase but is not able by itself to induce crossing over the G1-S boundary and consequently DNA synthesis. An increase in c-fos mRNA level was also induced by ADP but not by AMP or adenosine. Moreover, 2-methylthioadenosine 5'-triphosphate but not alpha, beta-methyleneadenosine 5'-triphosphate mediated this kind of response. Taken together, these results demonstrate that extracellular ATP induces the limited progression of arterial smooth muscle cells through the G1 phase via its fixation on P2 gamma receptors.
由于怀疑外源性ATP会影响增殖过程，因此通过研究细胞周期依赖性基因的mRNA稳态水平变化，来探讨其对动脉平滑肌细胞周期进程的影响。用外源性ATP刺激培养的静止平滑肌细胞，不仅诱导了即刻早期而且还诱导了延迟早期细胞周期依赖性基因的时序激活，这些基因通常在有丝分裂原刺激后表达。相比之下，ATP并没有增加G1晚期基因的mRNA水平，这表明这种核苷酸通过G1期诱导动脉平滑肌细胞的细胞周期进程有限，但自身无法诱导越过G1-S边界并因此无法诱导DNA合成。ADP也可诱导c-fos mRNA水平升高，但AMP或腺苷则不能。此外，2-甲硫基腺苷5'-三磷酸介导了这种反应，而α,β-亚甲基腺苷5'-三磷酸则不能。综上所述，这些结果表明，细胞外ATP通过其与P2γ受体的结合，诱导动脉平滑肌细胞通过G1期的有限进程。
