PANCREATIC EFFECTS OF ETHIONINE - BLOCKADE OF EXOCYTOSIS AND APPEARANCE OF CRINOPHAGY AND AUTOPHAGY PRECEDE CELLULAR NECROSIS
PANCREATIC EFFECTS OF ETHIONINE - BLOCKADE OF EXOCYTOSIS AND APPEARANCE OF CRINOPHAGY AND AUTOPHAGY PRECEDE CELLULAR NECROSIS
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DOI：
10.1152/ajpgi.1982.242.4.g297
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发表时间：
1982-01-01
影响因子：
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通讯作者：
MELDOLESI, J
中科院分区：
文献类型：
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作者：
KOIKE, H;STEER, ML;MELDOLESI, J
年轻的雌性小鼠喂食胆碱缺乏的、补充有乙硫氨酸（CDE）的饮食24小时后发生出血性胰腺坏死，5天死亡率约为百分之五十在饲料给药结束时，体内消化酶的释放被阻断，胞吐和腔膜再循环的图像消失，酶原颗粒积聚在腺泡细胞内。一般超微结构保存良好，蛋白质合成正常，分泌蛋白的细胞内转运仅轻微受阻。CDE饮食不影响膜融合-分裂的一般现象，但特异性抑制与胞吐作用相关的现象。撤去CDE饲料后（24小时），观察到酶原颗粒排入溶酶体（分泌吞噬），24小时后，观察到自噬作用。在胰腺坏死发生前不久，几乎正常外观的细胞分散在显示不同程度病变直至完全破裂的细胞中。CDE诱导的胰腺坏死是由一系列事件引起的：胞吐作用的阻断演变为分泌吞噬和自噬，这导致溶酶体激活酶原。
Young female mice fed a choline-deficient, ethionine-supplemented (CDE) diet for 24 h develop hemorrhagic pancreatic necrosis with a 5 day mortality rate of .apprx. 50%. At the end of the diet administration, the in vivo discharge of digestive enzymes was blocked, images of exocytosis and luminal membrane recycling disappeared and zymogen granules accumulated within acinar cells. The general ultrastructure remaind well preserved, protein synthesis was normal and intracellular transport of secretory proteins was only slightly retarded. The CDE diet did not affect the general phenomenon of membrane fusion-fission but specifically inhibited that associated with exocytosis. After withdrawal of the CDE diet (24 h), discharge of zymogen granules into lysosomes (crinophagy) was observed and, 24 h later, autophagocytosis was noted. Shortly before the onset of pancreatic necrosis, cells of nearly normal appearance were scattered among cells showing varying degrees of lesion up to complete disruption. The CDE-induced pancreatic necrosis resulted from a sequence of events: blockage of exocytosis evolved to crinophagy and autophagy, which led to lysosomal activation of zymogens.