Involvement of autophagy in trypsinogen activation within the pancreatic acinar cells.
Involvement of autophagy in trypsinogen activation within the pancreatic acinar cells.
复制标题
自噬参与胰腺腺泡细胞中胰蛋白酶原活化。
DOI：
10.1083/jcb.200712156
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发表时间：
2008-06-30
期刊：
影响因子：
--
通讯作者：
Yamamura K
中科院分区：
文献类型：
--
作者：
Hashimoto D;Ohmuraya M;Hirota M;Yamamoto A;Suyama K;Ida S;Okumura Y;Takahashi E;Kido H;Araki K;Baba H;Mizushima N;Yamamura K
自噬主要是细胞内的非选择性本体降解系统。最近的报道表明，根据疾病的阶段或周围的细胞环境，自噬可以作为细胞的保护者和杀伤者（综述参见Cuervo，A.M.2004. Trends Cell Biol.14：70-77）。我们发现，细胞质空泡诱导胰腺腺泡细胞的实验性胰腺炎是自噬的起源，微管相关蛋白1轻链3的表达和电子显微镜实验证明。为了分析大自噬在急性胰腺炎中的作用，我们制造了腺泡细胞中缺乏自噬相关基因5的条件性敲除小鼠。在条件性基因敲除小鼠中，除了在限制区域中出现非常轻微的水肿外，未观察到急性胰腺炎。出乎意料的是，胰蛋白酶原活化在没有自噬的情况下大大减少。这些结果表明，在急性胰腺炎的早期阶段，自噬通过将胰蛋白酶原递送到溶酶体而将胰蛋白酶原激活为胰蛋白酶，从而对胰腺腺泡细胞产生破坏性影响。
Autophagy is mostly a nonselective bulk degradation system within cells. Recent reports indicate that autophagy can act both as a protector and killer of the cell depending on the stage of the disease or the surrounding cellular environment (for review see Cuervo, A.M. 2004. Trends Cell Biol. 14:70–77). We found that cytoplasmic vacuoles induced in pancreatic acinar cells by experimental pancreatitis were autophagic in origin, as demonstrated by microtubule-associated protein 1 light chain 3 expression and electron microscopy experiments. To analyze the role of macroautophagy in acute pancreatitis, we produced conditional knockout mice lacking the autophagy-related 5 gene in acinar cells. Acute pancreatitis was not observed, except for very mild edema in a restricted area, in conditional knockout mice. Unexpectedly, trypsinogen activation was greatly reduced in the absence of autophagy. These results suggest that autophagy exerts devastating effects in pancreatic acinar cells by activation of trypsinogen to trypsin in the early stage of acute pancreatitis through delivering trypsinogen to the lysosome.
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影响因子：
64.8
作者：
Ichimura, Y;Kirisako, T;Ohsumi, Y
通讯作者：
Ohsumi, Y
影响因子：
3.3
作者：
Mizushima, N;Yamamoto, A;Ohsumi, Y
通讯作者：
Ohsumi, Y
DOI：
10.1083/jcb.200412022
发表时间：
2005-05-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Komatsu M;Waguri S;Ueno T;Iwata J;Murata S;Tanida I;Ezaki J;Mizushima N;Ohsumi Y;Uchiyama Y;Kominami E;Tanaka K;Chiba T
通讯作者：
Chiba T
影响因子：
64.8
作者：
Kuma, A;Hatano, M;Mizushima, N
通讯作者：
Mizushima, N
影响因子：
--
作者：
KOIKE, H;STEER, ML;MELDOLESI, J
通讯作者：
MELDOLESI, J