Gortat Anna, Sancho Mónica, Mondragón Laura, Messeguer Àngel, Pérez-Payá Enrique, Orzáez Mar
Laboratory of Peptide and Protein Chemistry, Centro de Investigación Príncipe Felipe, 46012, Valencia, Spain.
Department of Chemical and Biomolecular Nanotechnology, Instituto Química Avanzada de Cataluña (CSIC), 08034, Barcelona, Spain.
Protein Cell. 2015 Nov;6(11):833-43. doi: 10.1007/s13238-015-0200-2. Epub 2015 Sep 11.
The protein apoptotic protease activating factor 1 (Apaf1) is the central component of the apoptosome, a multiprotein complex that activates procaspase-9 after cytochrome c release from the mitochondria in the intrinsic pathway of apoptosis. We have developed a vital method that allows fluorescence-activated cell sorting of cells at different stages of the apoptotic pathway and demonstrated that upon pharmacological inhibition of Apaf1, cells recover from doxorubicin- or hypoxia-induced early apoptosis to normal healthy cell. Inhibiting Apaf1 not only prevents procaspase-9 activation but delays massive mitochondrial damage allowing cell recovery.
蛋白质凋亡蛋白酶激活因子1(Apaf1)是凋亡小体的核心成分,凋亡小体是一种多蛋白复合物,在细胞凋亡的内源性途径中,当细胞色素c从线粒体释放后,它会激活半胱天冬酶原-9。我们开发了一种重要方法,可对处于凋亡途径不同阶段的细胞进行荧光激活细胞分选,并证明在对Apaf1进行药理学抑制后,细胞可从阿霉素或缺氧诱导的早期凋亡恢复为正常健康细胞。抑制Apaf1不仅可防止半胱天冬酶原-9的激活,还能延迟大量线粒体损伤,从而使细胞得以恢复。