Quantitative organellar proteomics analysis of rough endoplasmic reticulum from normal and acute pancreatitis rat pancreas.

Quantitative organellar proteomics analysis of rough endoplasmic reticulum from normal and acute pancreatitis rat pancreas.
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DOI:
10.1021/pr900784c
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发表时间:
2010-02-05
影响因子:
4.4
通讯作者:
Williams, John A.
Williams, John A.
中科院分区:
生物学2区
文献类型:
--
作者:
Chen, Xuequn;Sans, Maria Dolors;Strahler, John R.;Karnovsky, Alla;Ernst, Stephen A.;Michailidis, George;Andrews, Philip C.;Williams, John A.

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粗面内质网(RER)是合成和加工消化酶的中枢细胞器,其功能改变可能参与急性胰腺炎(AP)的发病机制。为了全面表征正常和患病RER亚蛋白质组,本研究定量比较了正常和AP动物之间的蛋白质组成,使用同量异位素标签(iTRAQ)和二维LC-MALDI-MS/MS。共有469个独特的蛋白质,揭示了从四个独立的实验,使用两种不同的AP模型。这些蛋白质属于大量的功能类别,包括核糖体蛋白、易位子亚基、分子伴侣、分泌蛋白以及糖和脂质加工酶。37个RER蛋白(25个在马槟榔碱诱导的中是独特的,6个在雨蛙素诱导的中是独特的,6个在两种AP模型中是共同的)在AP期间显示出显著的变化,包括翻译调节因子和消化酶,而仅在一些ER伴侣蛋白中发现了轻微的变化。两种AP模型共有的六种蛋白质包括胰腺三酰甘油脂肪酶前体、Erp 27和脯氨酰4-羟化酶β多肽的减少以及纤维蛋白原α、β和γ链的急剧增加。这些结果表明,AP的早期阶段涉及多种RER蛋白的变化,可能会影响消化酶的合成和加工。
The rough endoplasmic reticulum (RER) is a central organelle for synthesizing and processing digestive enzymes and alteration of ER functions may participate in the pathogenesis of acute pancreatitis (AP). To comprehensively characterize the normal and diseased RER subproteome, this study quantitatively compared the protein compositions of pancreatic RER between normal and AP animals using isobaric tags (iTRAQ) and 2D LC-MALDI-MS/MS. A total of 469 unique proteins were revealed from four independent experiments using two different AP models. These proteins belong to a large number of functional categories including ribosomal proteins, translocon subunits, chaperones, secretory proteins, and glyco- and lipid-processing enzymes. 37 RER proteins (25 unique in arginine-induced, 6 unique in caerulein-induced and 6 common in both models of AP) showed significant changes during AP including translational regulators and digestive enzymes whereas only mild changes were found in some ER chaperones. The six proteins common to both AP models including a decrease in pancreatic triacylglycerol lipase precursor, Erp27, and prolyl 4-hydroxylase beta polypeptide as well as a dramatic increase in fibrinogen alpha, beta and gamma chains. These results suggest that the early stages of AP involve changes of multiple RER proteins that may affect the synthesis and processing of digestive enzymes.
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