Chow S C, Weis M, Kass G E, Holmström T H, Eriksson J E, Orrenius S
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
FEBS Lett. 1995 May 8;364(2):134-8. doi: 10.1016/0014-5793(95)00370-o.
The mechanism of Fas antigen-mediated apoptosis is at present unclear. We show here that the 100,000 x g supernatant from cell lysates prepared from anti-Fas-stimulated JUR-KAT T cells, induces chromatin fragmentation in isolated nuclei with concomitant morphological changes typically seen in apoptosis. The formation of this apoptotic nuclei promoting activity (ANPA) in JURKAT T cells after Fas antigen ligation was blocked by the serine protease inhibitors, TPCK and DCI, and by the interleukin 1-beta-converting enzyme inhibitor, VAD-FMK. In addition, chromatin degradation and morphological changes mediated by the ANPA in isolated nuclei were inhibited by TPCK, but not by DCI or VAD-FMK. These results suggest that Fas-mediated apoptosis in T cells involves the activation of a cascade of proteases.
目前尚不清楚Fas抗原介导的细胞凋亡机制。我们在此表明，抗Fas刺激的JUR-KAT T细胞制备的细胞裂解物经100,000×g离心后的上清液，可诱导分离细胞核中的染色质片段化，并伴有凋亡中常见的形态学变化。Fas抗原连接后JURKAT T细胞中这种凋亡细胞核促进活性（ANPA）的形成被丝氨酸蛋白酶抑制剂TPCK和DCI以及白细胞介素1-β转化酶抑制剂VAD-FMK所阻断。此外，TPCK可抑制ANPA介导的分离细胞核中的染色质降解和形态学变化，但DCI或VAD-FMK则不能。这些结果表明，T细胞中Fas介导的细胞凋亡涉及一系列蛋白酶的激活。
