Estimation of coupling factor 6-induced vascular damage and utilization for drug discovery

偶联因子6 （CF6）结合血管平滑肌细胞（VSMC）表面ATP合成酶的ss-sunbunit，通过ATP降解为ADP诱导质子流入细胞质。对血管紧张素II的反应，CF6诱导细胞外钙内流和细胞内游离钙浓度升高。与Wister Kyoto大鼠相比，自发性高血压大鼠（SHR）钙对CF6的反应性增强，经抗CF6- c末端抗体预处理后，钙对CF6的反应性被消除，提示CF6的c端参与了其肽的作用。在肠系膜动脉实验中，小动脉中的CF6通过激活酪氨酸激酶c-Src诱导血管紧张素II的收缩，并通过抗CF6- c末端抗体预处理减弱。总之，这些提示抑制CF6可能拮抗血管紧张素II作为肾素-血管紧张素系统的其他抑制剂的作用。

Coupling factor 6 (CF6) bound to ss-sunbunit of ATP synthase at the surface of vascular smooth muscle cells (VSMC), and induced proton influx into the cytoplasm via degradation of ATP to ADP. CF6 induced influx of extracellular calcium and increased intracellular free calcium concentration in response to angiotensin II. These responsiveness of calcium to CF6 was enhanced in spontaneously hypertensive rats (SHR) compared with Wister Kyoto rats, and were abolished after pretreatment with anti-CF6-C terminus antibody, suggesting that the C-terminus of CF6 is involved in the action of its peptide. In the experiment of mesenteric arteries, CF6 in the arteriole induced the contraction in response to angiotensin II via activation of tyrosine kinase c-Src, and it was attenuated by pretreatment with anti-CF6-C terminus antibody. Overall, these suggest that inhibition of CF6 may antagonize the action of angiotensin II as other inhibitors of rennin-angiotensin system.