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使用聚乙二醇化精氨酸脱亚氨酶诱导小鼠全身自噬并增加能量代谢的方案。

A protocol to induce systemic autophagy and increase energy metabolism in mice using PEGylated arginine deiminase.

机构信息

Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.

Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Cell Biology & Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA.

出版信息

STAR Protoc. 2022 Sep 16;3(3):101489. doi: 10.1016/j.xpro.2022.101489. Epub 2022 Jun 23.

DOI:10.1016/j.xpro.2022.101489
PMID:35776644
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9249829/
Abstract

Obesity is a prevalent metabolic disorder worldwide. Here, we describe a comprehensive protocol using pegylated arginine deiminase (ADI-EPG 20) to apply the concept that arginine depletion induces systemic autophagy to drive whole-body energy metabolism and weight loss in mice. We detail the steps for cohort setup, mouse husbandry, and treatment and provide expected results under these conditions. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2022a, 2022b).

摘要

肥胖是一种普遍存在的代谢紊乱全球范围内。在这里，我们描述了一个使用聚乙二醇化精氨酸脱亚氨酶（ADI-EPG 20）的综合方案，该方案应用了精氨酸耗竭诱导全身自噬的概念，以驱动小鼠的全身能量代谢和体重减轻。我们详细介绍了队列设置、小鼠饲养和治疗的步骤，并提供了在这些条件下的预期结果。有关使用和执行此方案的完整详细信息，请参阅 Zhang 等人（2022a，2022b）。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54ac/9249829/ebd70026eeb5/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54ac/9249829/9ab79a1abd39/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54ac/9249829/fa947bac796b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54ac/9249829/3ad4b3f35b47/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54ac/9249829/f668d2fb7d03/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54ac/9249829/08285c15e6e0/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54ac/9249829/ebd70026eeb5/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54ac/9249829/9ab79a1abd39/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54ac/9249829/fa947bac796b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54ac/9249829/3ad4b3f35b47/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54ac/9249829/f668d2fb7d03/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54ac/9249829/08285c15e6e0/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54ac/9249829/ebd70026eeb5/gr5.jpg

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本文引用的文献

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Driving arginine catabolism to activate systemic autophagy.驱动精氨酸分解代谢以激活全身自噬。
Autophagy Rep. 2022;1(1):65-69. doi: 10.1080/27694127.2022.2040763. Epub 2022 Mar 24.
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Arginine deprivation alters microglial polarity and synergizes with radiation to eradicate non-arginine-auxotrophic glioblastoma tumors.精氨酸剥夺改变小胶质细胞极性，并与放射治疗协同作用根除非精氨酸营养缺陷型神经胶质瘤肿瘤。
J Clin Invest. 2022 Mar 15;132(6). doi: 10.1172/JCI142137.
3
Pegylated arginine deiminase drives arginine turnover and systemic autophagy to dictate energy metabolism.
聚乙二醇化精氨酸脱亚氨酶驱动精氨酸代谢周转和全身自噬来调控能量代谢。
Cell Rep Med. 2022 Jan 18;3(1):100498. doi: 10.1016/j.xcrm.2021.100498.
4
Nestlet Shredding and Nest Building Tests to Assess Features of Psychiatric Disorders in Mice.用于评估小鼠精神疾病特征的巢材撕碎和筑巢测试
Bio Protoc. 2020 Dec 20;10(24). doi: 10.21769/BioProtoc.3863.
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Arginine Depletion Therapy with ADI-PEG20 Limits Tumor Growth in Argininosuccinate Synthase-Deficient Ovarian Cancer, Including Small-Cell Carcinoma of the Ovary, Hypercalcemic Type.精氨酸耗竭疗法联合 ADI-PEG20 抑制精氨琥珀酸合成酶缺陷型卵巢癌（包括卵巢小细胞癌、高钙血症型）的肿瘤生长。
Clin Cancer Res. 2020 Aug 15;26(16):4402-4413. doi: 10.1158/1078-0432.CCR-19-1905. Epub 2020 May 14.
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Phase III randomized study of second line ADI-PEG 20 plus best supportive care versus placebo plus best supportive care in patients with advanced hepatocellular carcinoma.ADI-PEG 20 二线治疗联合最佳支持治疗对比安慰剂联合最佳支持治疗晚期肝细胞癌的 III 期随机研究。
Ann Oncol. 2018 Jun 1;29(6):1402-1408. doi: 10.1093/annonc/mdy101.
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A Phase II Study of Arginine Deiminase (ADI-PEG20) in Relapsed/Refractory or Poor-Risk Acute Myeloid Leukemia Patients.精氨酸脱亚氨酶（ADI-PEG20）治疗复发/难治或高危急性髓系白血病患者的 II 期研究。
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