Arginine depletion by arginine deiminase does not affect whole protein metabolism or muscle fractional protein synthesis rate in mice.
Arginine depletion by arginine deiminase does not affect whole protein metabolism or muscle fractional protein synthesis rate in mice.
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DOI：
10.1371/journal.pone.0119801
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Didelija IC
中科院分区：
文献类型：
--
作者：
Marini JC;Didelija IC
由于某些癌细胞对精氨酸的绝对需求，精氨酸消耗是临床试验中用于治疗多种癌症的一种疗法。精氨酸是一种氨基酸，不仅用作其他重要分子的前体，而且还用于蛋白质合成。由于精氨酸消耗可能会加剧癌症患者的体重（尤其是去脂体重）的逐渐减少，因此我们确定了聚乙二醇化精氨酸脱亚胺酶 (ADI-PEG 20) 精氨酸消耗对小鼠多个组织中全身蛋白质合成和部分蛋白质合成率的影响。 ADI-PEG 20 成功耗尽循环精氨酸 (<1 μmol/L)，并将瓜氨酸浓度提高十倍以上。然而，体重和身体成分不受 ADI-PEG 20 的影响。尽管精氨酸耗尽，但 ADI-PEG 20 治疗的小鼠全身蛋白质合成和分解得以维持。肌肉的蛋白质合成率分数也不受精氨酸消耗的影响。大多数组织（肝、肾、脾、心、肺、胃、小肠和大肠、胰腺）能够维持其蛋白质合成率；然而，由于 ADI-PEG 20 治疗，大脑、胸腺和睾丸的蛋白质合成率有所降低。此外，这些结果通过脲基[14C]瓜氨酸的掺入得到证实，这表明局部转化为精氨酸，进入蛋白质。总之，瓜氨酸的细胞内循环途径能够提供足够的精氨酸来维持蛋白质合成率并防止去脂体重和体重的损失。
Due to the absolute need for arginine that certain cancer cells have, arginine depletion is a therapy in clinical trials to treat several types of cancers. Arginine is an amino acids utilized not only as a precursor for other important molecules, but also for protein synthesis. Because arginine depletion can potentially exacerbate the progressive loss of body weight, and especially lean body mass, in cancer patients we determined the effect of arginine depletion by pegylated arginine deiminase (ADI-PEG 20) on whole body protein synthesis and fractional protein synthesis rate in multiple tissues of mice. ADI-PEG 20 successfully depleted circulating arginine (<1 μmol/L), and increased citrulline concentration more than tenfold. Body weight and body composition, however, were not affected by ADI-PEG 20. Despite the depletion of arginine, whole body protein synthesis and breakdown were maintained in the ADI-PEG 20 treated mice. The fractional protein synthesis rate of muscle was also not affected by arginine depletion. Most tissues (liver, kidney, spleen, heart, lungs, stomach, small and large intestine, pancreas) were able to maintain their fractional protein synthesis rate; however, the fractional protein synthesis rate of brain, thymus and testicles was reduced due to the ADI-PEG 20 treatment. Furthermore, these results were confirmed by the incorporation of ureido [14C]citrulline, which indicate the local conversion into arginine, into protein. In conclusion, the intracellular recycling pathway of citrulline is able to provide enough arginine to maintain protein synthesis rate and prevent the loss of lean body mass and body weight.
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影响因子：
--
作者：
FEATHERSTON, WR;ROGERS, QR;FREEDLAND, RA
通讯作者：
FREEDLAND, RA
影响因子：
3.4
作者：
Ott, Patrick A.;Carvajal, Richard D.;Pandit-Taskar, Neeta;Jungbluth, Achim A.;Hoffman, Eric W.;Wu, Bor-Wen;Bomalaski, John S.;Venhaus, Ralph;Pan, Linda;Old, Lloyd J.;Pavlick, Anna C.;Wolchok, Jedd D.
通讯作者：
Wolchok, Jedd D.
影响因子：
4.2
作者：
Brosnan, ME;Brosnan, JT
通讯作者：
Brosnan, JT
影响因子：
4.2
作者：
Matthews, Dwight E.
通讯作者：
Matthews, Dwight E.
影响因子：
4.2
作者：
Marini, Juan C.
通讯作者：
Marini, Juan C.