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膜结合型泛酰巯基乙胺酶-1的泛酰巯基乙胺酶活性:泛酰巯基乙胺酶-1缺陷小鼠组织中缺乏游离半胱胺。

Pantetheinase activity of membrane-bound Vanin-1: lack of free cysteamine in tissues of Vanin-1 deficient mice.

作者信息

Pitari G, Malergue F, Martin F, Philippe J M, Massucci M T, Chabret C, Maras B, Duprè S, Naquet P, Galland F

机构信息

Dipartmento di Biologia di Base ed Applicata Università di L'Aquila, Italy.

出版信息

FEBS Lett. 2000 Oct 20;483(2-3):149-54. doi: 10.1016/s0014-5793(00)02110-4.

DOI:10.1016/s0014-5793(00)02110-4
PMID:11042271
Abstract

Pantetheinase (EC 3.5.1.-) is an ubiquitous enzyme which in vitro has been shown to recycle pantothenic acid (vitamin B5) and to produce cysteamine, a potent anti-oxidant. We show that the Vanin-1 gene encodes pantetheinase widely expressed in mouse tissues: (1) a pantetheinase activity is specifically expressed by Vanin-1 transfectants and is immunodepleted by specific antibodies; (2) Vanin-1 is a GPI-anchored pantetheinase, and consequently an ectoenzyme; (3) Vanin-1 null mice are deficient in membrane-bound pantetheinase activity in kidney and liver; (4) in these organs, a major metabolic consequence is the absence of detectable free cysteamine; this demonstrates that membrane-bound pantetheinase is the main source of cysteamine in tissues under physiological conditions. Since the Vanin-1 molecule was previously shown to be involved in the control of thymus reconstitution following sublethal irradiation in vivo, this raises the possibility that Vanin/pantetheinase might be involved in the regulation of some immune functions maybe in the context of the response to oxidative stress.

摘要

泛硫乙胺酶(EC 3.5.1.-)是一种普遍存在的酶,在体外已被证明可循环利用泛酸(维生素B5)并产生半胱胺,一种有效的抗氧化剂。我们发现Vanin-1基因编码的泛硫乙胺酶在小鼠组织中广泛表达:(1)泛硫乙胺酶活性由Vanin-1转染子特异性表达,并被特异性抗体免疫清除;(2)Vanin-1是一种糖基磷脂酰肌醇锚定的泛硫乙胺酶,因此是一种外切酶;(3)Vanin-1基因敲除小鼠的肾脏和肝脏中膜结合泛硫乙胺酶活性缺乏;(4)在这些器官中,一个主要的代谢后果是未检测到游离半胱胺;这表明膜结合泛硫乙胺酶是生理条件下组织中半胱胺的主要来源。由于先前已证明Vanin-1分子参与体内亚致死剂量照射后胸腺重建的控制,这增加了Vanin/泛硫乙胺酶可能参与某些免疫功能调节的可能性,也许是在对氧化应激的反应背景下。

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