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接受手术的非恶病质荷瘤小鼠全身及器官水平的蛋白质分解代谢

Protein breakdown on whole-body and organ level in non-cachectic tumour-bearing mice undergoing surgery.

作者信息

Vissers Yvonne L J, von Meyenfeldt Maarten F, Argilés Josep M, Luiking Yvette C, Dejong Cornelis H C, Deutz Nicolaas E P

机构信息

Department of Surgery, Maastricht University and University Hospital Maastricht, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), The Netherlands.

出版信息

Clin Nutr. 2007 Aug;26(4):483-90. doi: 10.1016/j.clnu.2007.03.005. Epub 2007 May 21.

Abstract

BACKGROUND & AIMS: Since both cancer and surgery are known to alter protein turnover, we investigated how the presence of tumour affects post-operative protein breakdown.

METHODS

Controls and tumour-bearing non-cachectic mice were studied, both with and without laparotomy (n=8 per group). One day after laparotomy, stable isotopes of phenylalanine and 3-methylhistidine were used in a steady-state protocol to assess total protein breakdown on whole-body level and in muscle, intestines, liver and kidney, in addition to whole-body myofibrillar protein breakdown and body composition. Proteasomal chymotrypsin-like activity was measured to determine activity of the ATP-dependent ubiquitin pathway.

RESULTS

On whole-body level, the presence of tumour increased total protein breakdown from 47+/-6 to 58+/-4 nmol/10 g/min (p<0.05) and myofibrillar protein breakdown from 0.70+/-0.04 to 1.22+/-0.14 nmol/10 g/min (p<0.05) without affecting protein breakdown in organs, body composition or proteasomal activity. Laparotomy increased myofibrillar protein breakdown in controls (from 0.70+/-0.04 to 0.98+/-0.12 nmol/10 g/min, p<0.05) and tumour-bearing mice (from 1.22+/-0.14 to 1.54+/-0.22 nmol/10 g/min, p=0.15) to a similar extent.

CONCLUSIONS

Whole-body total protein breakdown, total protein breakdown across organs, body composition or proteasomal activity were not affected by laparotomy. Tumour-bearing mice had increased total and myofibrillar protein breakdown on whole-body level even before weight loss was obvious. However, this did not affect the post-operative response in protein breakdown or body composition.

摘要

背景与目的

由于已知癌症和手术都会改变蛋白质周转率,我们研究了肿瘤的存在如何影响术后蛋白质分解。

方法

对对照组和荷瘤非恶病质小鼠进行研究,每组均分为开腹组和未开腹组(每组8只)。开腹术后一天,采用苯丙氨酸和3-甲基组氨酸的稳定同位素,通过稳态方案评估全身水平以及肌肉、肠道、肝脏和肾脏中的总蛋白质分解,同时评估全身肌原纤维蛋白分解和身体组成。测量蛋白酶体类胰凝乳蛋白酶样活性以确定ATP依赖的泛素途径的活性。

结果

在全身水平上,肿瘤的存在使总蛋白质分解从47±6增加至58±4 nmol/10 g/分钟(p<0.05),肌原纤维蛋白分解从0.70±0.04增加至1.22±0.14 nmol/10 g/分钟(p<0.05),而不影响各器官的蛋白质分解、身体组成或蛋白酶体活性。开腹术使对照组(从0.70±0.04增加至0.98±0.12 nmol/10 g/分钟,p<0.05)和荷瘤小鼠(从1.22±0.14增加至1.54±0.22 nmol/10 g/分钟,p=0.15)的肌原纤维蛋白分解增加到相似程度。

结论

开腹术不影响全身总蛋白质分解、各器官的总蛋白质分解、身体组成或蛋白酶体活性。荷瘤小鼠在体重明显减轻之前,全身总蛋白质分解和肌原纤维蛋白分解就已增加。然而,这并不影响术后蛋白质分解或身体组成的反应。

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