Role of non-protein amino acid L-canavanine in autoimmunity
Role of non-protein amino acid L-canavanine in autoimmunity
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DOI：
10.1016/j.autrev.2005.12.004
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发表时间：
2006-07-01
影响因子：
13.6
通讯作者：
Satoh, Minoru
中科院分区：
文献类型：
--
作者：
Akaogi, Jun;Barker, Tolga;Satoh, Minoru
SLE和苜蓿的关联首次在一名志愿者中报道，该志愿者在高胆固醇血症研究中摄入苜蓿种子时发生了狼疮样自身免疫。这一点得到了用苜蓿芽喂养的猴子患SLE的研究的证实。用L-刀豆氨酸再激发使疾病复发。存在于苜蓿中的精氨酸同系物L-刀豆氨酸被怀疑是一个原因。L-刀豆氨酸可以通过乙酰氨基转移RNA合成酶在蛋白质合成过程中取代L-精氨酸。异常刀豆蛋白具有破坏的结构和功能。在少数病例中报告的苜蓿片诱导或加重SLE仍存在争议。关于苜蓿与SLE关系的流行病学研究很少。在小鼠中，用L-刀豆氨酸喂养的NZB/W F1、NZB和DBA/2小鼠显示出SLE的恶化/触发，然而，BALB/c研究是阴性的。L-刀豆氨酸诱导的凋亡细胞可以被吞噬，并且是内体蛋白酶加工的自身抗原的来源。内源性刀豆蛋白被泛素化并通过蛋白酶体加工。L-刀豆氨酸掺入蛋白酶体或内体也可导致抗原加工的破坏。丙氨酸/L-刀豆氨酸诱导的狼疮将是一种有趣的自身免疫模型，其通过在翻译水平上修饰自身蛋白而诱导。(c)2005 Elsevier B. V.保留所有权利。
Association of SLE and alfalfa was first reported in a volunteer who developed lupus-like autoimmunity while ingesting alfalfa seed for a hypercholesterolemia study. This was corroborated with studies in monkeys fed with alfalfa sprout that developed SLE. Re-challenge with L-canavanine relapsed the disease. Arginine homologue L-canavanine, present in alfalfa, was suspected as a cause. L-canavanine can be charged by arginyl tRNA synthetase to replace L-arginine during protein synthesis. Aberrant canavanyl proteins have disrupted structure and functions. Induction or exacerbation of SLE by alfalfa tablets reported in a few cases remains controversial. Epidemiological studies on the relationship between alfalfa and SLE are sparse. In mice, NZB/W F1, NZB, and DBA/2 mice fed with L-canavanine show exacerbation/triggering of the SLE, however, BALB/c studies were negative.L-canavanine incorporation may be more efficient in the presence of inflammation or other conditions that can cause arginine deficiency. The L-canavanine induced apoptotic cells can be phagocytosed and a source of autoantigens processed by endosomal proteases. Endogenous canavanyl proteins are ubiquitinated and processed via proteasome. Incorporation Of L-canavanine into proteasome or endosome can also cause disruption of antigen processing. Alfalfa/L-canavanine-induced lupus will bean interesting model of autoimmunity induced by the modification of self-proteins at the translational level. (c) 2005 Elsevier B.V. All rights reserved.