Purification and cloning of an apoptosis-inducing protein derived from fish infected with Anisakis simplex, a causative nematode of human anisakiasis

Purification and cloning of an apoptosis-inducing protein derived from fish infected with Anisakis simplex, a causative nematode of human anisakiasis
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DOI:
10.4049/jimmunol.165.3.1491
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发表时间:
2000-08-01
影响因子:
4.4
通讯作者:
Yonehara, S
Yonehara, S
中科院分区:
医学2区
文献类型:
--
作者:
Jung, SK;Mai, A;Yonehara, S

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在研究海产品对细胞生长的影响时,我们发现,一种海洋鱼类鲭鱼的内脏提取物对多种哺乳动物肿瘤细胞具有强大的和剂量依赖性的凋亡诱导作用。这种活性明显依赖于C.鲭鱼与幼虫线虫,简单异尖线虫。在纯化了具有诱导烟草枯萎活性的蛋白后,我们克隆了相应的基因,发现它是一个黄素蛋白。这种蛋白质,被称为骨化诱导蛋白(AIP),也被发现具有内质网滞留信号(C-末端KDEL序列)和过氧化氢产生活性,表明我们已经分离出一种新的具有强效骨化诱导活性的reticuloplasmin。AIP仅在感染线虫幼虫后才被诱导,并定位于幼虫周围形成的囊,以防止其迁移到宿主组织。我们的研究结果表明,AIP可能具有阻止线虫感染的功能。
While investigating the effect of marine products on cell growth, we found that visceral extracts of Chub mackerel, an ocean fish, had a powerful and dose-dependent apoptosis-inducing effect on a variety of mammalian tumor cells. This activity was strikingly dependent on infection of the C. mackerel with the larval nematode, Anisakis simplex. After purification of the protein responsible for the apoptosis-inducing activity, we cloned the corresponding gene and found it to be a flavoprotein. This protein, termed apoptosis-inducing protein (AIP), was also found to possess an endoplasmic reticulum retention signal (C-terminal KDEL sequence) and H2O2-producing activity, indicating that we had isolated a novel reticuloplasimin with potent apoptosis-inducing activity. AIP was induced in fish only after infection with larval nematode and was localized to capsules that formed around larvae to prevent their migration to host tissues, Our results suggest that AIP may function to impede nematode infection.