Lysosomal chymotrypsin B potentiates apoptosis via cleavage of Bid
Lysosomal chymotrypsin B potentiates apoptosis via cleavage of Bid
复制标题
溶酶体糜蛋白酶 B 通过 Bid 裂解增强细胞凋亡
DOI：
10.1007/s00018-010-0356-0
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发表时间：
2010-08-01
影响因子：
8
通讯作者：
Yang, Fuyu
中科院分区：
文献类型：
--
作者：
Zhao, Kai;Zhao, Xingyu;Yang, Fuyu
胰凝乳蛋白酶B（CtrB）不仅是一种消化酶，而且还存在于溶酶体中。在此，我们证明了CtrB的广泛分布，并探讨了CtrB在细胞凋亡中的参与。RH-35细胞暴露于H2O2或棕榈酸诱导溶酶体CtrB重新分布到细胞质中作为溶酶体膜透化（LMP）的结果。抑制CtrB可显著阻断细胞凋亡，而过表达CtrB可显著敏化细胞凋亡。CtrB在中性条件下能裂解Bid。在Bid沉默的RH-35细胞中，CtrB蛋白诱导的细胞凋亡减弱，提示CtrB蛋白主要通过加工Bid介导RH-35细胞凋亡。我们的数据还表明，LMP发生早于线粒体外膜透化; Bid激活启动caspase-8可能会加强CtrB的LMP的结果，这会导致一个正反馈回路，导致tBid的积累，并导致溶酶体和线粒体依赖性细胞凋亡。
We have reported that chymotrypsin B (CtrB) is not just a digestive enzyme but is also stored in lysosomes. Herein, we demonstrated a broad distribution of CtrB and explored the involvement of CtrB in apoptosis. Exposure of RH-35 cells to H2O2or palmitate induced the redistribution of lysosomal CtrB into the cytoplasm as a result of lysosomal membrane permeabilization (LMP). Suppression of CtrB significantly blocked apoptosis, while overexpression of CtrB sensitized apoptosis markedly. CtrB could cleave Bid under neutral conditions. In RH-35 cells with Bid silenced, apoptosis induced by CtrB protein was attenuated, suggesting that CtrB mediates apoptosis of RH-35 cells mainly through processing Bid. Our data also suggest that LMP occurs earlier than mitochondrial outer membrane permeabilization; Bid activation initiated by caspase-8 might be reinforced by CtrB in consequence of LMP, which causes a positive feedback loop leading to the accumulation of tBid, and results in lysosome- and mitochondrion-dependent apoptosis.