体内凋亡途径中半胱天冬酶9的差异需求。

Differential requirement for caspase 9 in apoptotic pathways in vivo.

作者信息

Hakem R, Hakem A, Duncan G S, Henderson J T, Woo M, Soengas M S, Elia A, de la Pompa J L, Kagi D, Khoo W, Potter J, Yoshida R, Kaufman S A, Lowe S W, Penninger J M, Mak T W

机构信息

Amgen Institute, Toronto, Ontario, Canada.

出版信息

Cell. 1998 Aug 7;94(3):339-52. doi: 10.1016/s0092-8674(00)81477-4.

DOI:10.1016/s0092-8674(00)81477-4

PMID:9708736

Abstract

Mutation of Caspase 9 (Casp9) results in embryonic lethality and defective brain development associated with decreased apoptosis. Casp9-/- embryonic stem cells and embryonic fibroblasts are resistant to several apoptotic stimuli, including UV and gamma irradiation. Casp9-/- thymocytes are also resistant to dexamethasone- and gamma irradiation-induced apoptosis, but are surprisingly sensitive to apoptosis induced by UV irradiation or anti-CD95. Resistance to apoptosis is accompanied by retention of the mitochondrial membrane potential in mutant cells. In addition, cytochrome c is translocated to the cytosol of Casp9-/- ES cells upon UV stimulation, suggesting that Casp9 acts downstream of cytochrome c. Caspase processing is inhibited in Casp9-/- ES cells but not in thymocytes or splenocytes. Comparison of the requirement for Casp9 and Casp3 in different apoptotic settings indicates the existence of at least four different apoptotic pathways in mammalian cells.

摘要

半胱天冬酶9（Casp9）的突变导致胚胎致死，并伴有凋亡减少相关的脑发育缺陷。Casp9基因敲除的胚胎干细胞和胚胎成纤维细胞对多种凋亡刺激具有抗性，包括紫外线和γ射线照射。Casp9基因敲除的胸腺细胞对糖皮质激素和γ射线诱导的凋亡也具有抗性，但令人惊讶的是，它们对紫外线照射或抗CD95诱导的凋亡敏感。对凋亡的抗性伴随着突变细胞中线粒体膜电位的保留。此外，紫外线刺激后，细胞色素c会转移至Casp9基因敲除的胚胎干细胞的细胞质中，这表明Casp9在细胞色素c的下游起作用。半胱天冬酶的加工在Casp9基因敲除的胚胎干细胞中受到抑制，但在胸腺细胞或脾细胞中不受抑制。对不同凋亡环境中Casp9和Casp3需求的比较表明，哺乳动物细胞中至少存在四种不同的凋亡途径。