弗林蛋白酶抑制剂六聚-D-精氨酸可在体内阻断铜绿假单胞菌外毒素A的激活。
The furin inhibitor hexa-D-arginine blocks the activation of Pseudomonas aeruginosa exotoxin A in vivo.
作者信息
Sarac Miroslav S, Cameron Angus, Lindberg Iris
机构信息
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, New Orleans 70112, USA.
出版信息
Infect Immun. 2002 Dec;70(12):7136-9. doi: 10.1128/IAI.70.12.7136-7139.2002.
Abstract
The Pseudomonas aeruginosa exotoxin A (PEA) protein requires furin-mediated cleavage for manifestation of toxicity. We show here that the small stable furin inhibitor hexa-D-arginine amide effectively blocks PEA-induced cell lysis and is itself noncytotoxic. Administration of hexa-D-arginine to PEA-treated mice significantly improves their survival rate and also decreases circulating levels of tumor necrosis factor alpha.
摘要
铜绿假单胞菌外毒素A（PEA）蛋白需要弗林蛋白酶介导的切割才能表现出毒性。我们在此表明，小的稳定弗林蛋白酶抑制剂六-D-精氨酸酰胺可有效阻断PEA诱导的细胞裂解，且其本身无细胞毒性。给经PEA处理的小鼠施用六-D-精氨酸可显著提高其存活率，并降低肿瘤坏死因子α的循环水平。
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The furin inhibitor hexa-D-arginine blocks the activation of Pseudomonas aeruginosa exotoxin A in vivo.弗林蛋白酶抑制剂六聚-D-精氨酸可在体内阻断铜绿假单胞菌外毒素A的激活。
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本文引用的文献
1
Polyarginines are potent furin inhibitors.聚精氨酸是有效的弗林蛋白酶抑制剂。
J Biol Chem. 2000 Nov 24;275(47):36741-9. doi: 10.1074/jbc.M003848200.
2
Paradoxical synergistic effects of tumour necrosis factor and interleukin 1 in murine gut-derived sepsis with Pseudomonas aeruginosa.肿瘤坏死因子与白细胞介素-1在小鼠铜绿假单胞菌肠道源性脓毒症中的矛盾协同效应
Cytokine. 1999 May;11(5):366-72. doi: 10.1006/cyto.1998.0434.
3
Bi-cycling the furin pathway: from TGN localization to pathogen activation and embryogenesis.双循环弗林蛋白酶途径：从反式高尔基体网络定位到病原体激活和胚胎发育
Trends Cell Biol. 1999 Jan;9(1):28-35. doi: 10.1016/s0962-8924(98)01382-8.
4
Acute hepatotoxicity of Pseudomonas aeruginosa exotoxin A in mice depends on T cells and TNF.铜绿假单胞菌外毒素A对小鼠的急性肝毒性取决于T细胞和肿瘤坏死因子。
J Immunol. 1998 Nov 15;161(10):5745-54.
5
alpha1-Antitrypsin Portland, a bioengineered serpin highly selective for furin: application as an antipathogenic agent.α1-抗胰蛋白酶波特兰，一种对弗林蛋白酶具有高度选择性的生物工程丝氨酸蛋白酶抑制剂：作为抗病原体剂的应用。
Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7293-8. doi: 10.1073/pnas.95.13.7293.
6
Furin: a mammalian subtilisin/Kex2p-like endoprotease involved in processing of a wide variety of precursor proteins.弗林蛋白酶：一种哺乳动物枯草杆菌蛋白酶/Kex2p样内切蛋白酶，参与多种前体蛋白的加工。
Biochem J. 1997 Nov 1;327 ( Pt 3)(Pt 3):625-35. doi: 10.1042/bj3270625.
7
Furin-mediated cleavage of Pseudomonas exotoxin-derived chimeric toxins.弗林蛋白酶介导的铜绿假单胞菌外毒素衍生嵌合毒素的切割。
J Biol Chem. 1997 Dec 12;272(50):31707-11. doi: 10.1074/jbc.272.50.31707.
8
Furin regulates both the activation of Pseudomonas exotoxin A and the Quantity of the toxin receptor expressed on target cells.弗林蛋白酶既调节铜绿假单胞菌外毒素A的激活，又调节靶细胞上表达的毒素受体数量。
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9
10
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Infect Immun. 1994 Feb;62(2):333-40. doi: 10.1128/iai.62.2.333-340.1994.
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