Suppr超能文献

半胱胺,泛酸酶的天然代谢产物,对疟原虫表现出特异性活性。

Cysteamine, the natural metabolite of pantetheinase, shows specific activity against Plasmodium.

机构信息

Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montréal, QC, Canada.

出版信息

Exp Parasitol. 2010 Aug;125(4):315-24. doi: 10.1016/j.exppara.2010.02.009. Epub 2010 Feb 26.

Abstract

In mice, loss of pantetheinase activity causes susceptibility to infection with Plasmodium chabaudi AS. Treatment of mice with the pantetheinase metabolite cysteamine reduces blood-stage replication of P. chabaudi and significantly increases survival. Similarly, a short exposure of Plasmodium to cysteamine ex vivo is sufficient to suppress parasite infectivity in vivo. This effect of cysteamine is specific and not observed with a related thiol (dimercaptosuccinic acid) or with the pantethine precursor of cysteamine. Also, cysteamine does not protect against infection with the parasite Trypanosoma cruzi or the fungal pathogen Candida albicans, suggesting cysteamine acts directly against the parasite and does not modulate host inflammatory response. Cysteamine exposure also blocks replication of P. falciparum in vitro; moreover, these treated parasites show higher levels of intact hemoglobin. This study highlights the in vivo action of cysteamine against Plasmodium and provides further evidence for the involvement of pantetheinase in host response to this infection.

摘要

在小鼠中,泛酰巯基乙胺酶活性的丧失会导致对疟原虫 chabaudi AS 的易感性。用泛酰巯基乙胺酶代谢物半胱胺治疗小鼠可降低疟原虫的血期复制,并显著提高存活率。同样,体外短时间接触半胱胺足以抑制体内寄生虫的感染力。半胱胺的这种作用是特异性的,与相关的硫醇(二巯基丁二酸)或半胱胺的泛酰巯基乙胺前体都没有观察到这种作用。此外,半胱胺不能预防寄生虫克氏锥虫或真菌病原体白色念珠菌的感染,这表明半胱胺直接作用于寄生虫,而不调节宿主炎症反应。半胱胺暴露也可阻断体外疟原虫 falciparum 的复制;此外,这些经过处理的寄生虫显示出更高水平的完整血红蛋白。本研究强调了半胱胺在体内对疟原虫的作用,并进一步证明了泛酰巯基乙胺酶参与宿主对这种感染的反应。

相似文献

1
Cysteamine, the natural metabolite of pantetheinase, shows specific activity against Plasmodium.
Exp Parasitol. 2010 Aug;125(4):315-24. doi: 10.1016/j.exppara.2010.02.009. Epub 2010 Feb 26.
3
Cysteamine, the molecule used to treat cystinosis, potentiates the antimalarial efficacy of artemisinin.
Antimicrob Agents Chemother. 2010 Aug;54(8):3262-70. doi: 10.1128/AAC.01719-09. Epub 2010 May 17.
4
Violacein extracted from Chromobacterium violaceum inhibits Plasmodium growth in vitro and in vivo.
Antimicrob Agents Chemother. 2009 May;53(5):2149-52. doi: 10.1128/AAC.00693-08. Epub 2009 Mar 9.
5
The effect of nitric oxide on the growth of Plasmodium falciparum, P. chabaudi and P. berghei in vitro.
Parasite Immunol. 2000 Feb;22(2):97-106. doi: 10.1046/j.1365-3024.2000.00281.x.
6
Genetic analysis in mice identifies cysteamine as a novel partner for artemisinin in the treatment of malaria.
Mamm Genome. 2011 Aug;22(7-8):486-94. doi: 10.1007/s00335-011-9316-8. Epub 2011 Mar 25.
9
BDA-410: a novel synthetic calpain inhibitor active against blood stage malaria.
Mol Biochem Parasitol. 2007 Sep;155(1):26-32. doi: 10.1016/j.molbiopara.2007.05.004. Epub 2007 May 18.
10
Synergy of the antiretroviral protease inhibitor indinavir and chloroquine against malaria parasites in vitro and in vivo.
Parasitol Res. 2011 Dec;109(6):1519-24. doi: 10.1007/s00436-011-2427-z. Epub 2011 May 3.

引用本文的文献

3
Forward Genetics in Apicomplexa Biology: The Host Side of the Story.
Front Cell Infect Microbiol. 2022 May 12;12:878475. doi: 10.3389/fcimb.2022.878475. eCollection 2022.
4
Surveying the Vampire Bat () Serum Proteome: A Resource for Identifying Immunological Proteins and Detecting Pathogens.
J Proteome Res. 2021 May 7;20(5):2547-2559. doi: 10.1021/acs.jproteome.0c00995. Epub 2021 Apr 10.
5
The Pathophysiological Role of CoA.
Int J Mol Sci. 2020 Nov 28;21(23):9057. doi: 10.3390/ijms21239057.
6
Regulation of coenzyme A levels by degradation: the 'Ins and Outs'.
Prog Lipid Res. 2020 Apr;78:101028. doi: 10.1016/j.plipres.2020.101028. Epub 2020 Mar 29.
7
Therapeutic Applications of Cysteamine and Cystamine in Neurodegenerative and Neuropsychiatric Diseases.
Front Neurol. 2019 Dec 12;10:1315. doi: 10.3389/fneur.2019.01315. eCollection 2019.
8
Host genetics in malaria: lessons from mouse studies.
Mamm Genome. 2018 Aug;29(7-8):507-522. doi: 10.1007/s00335-018-9744-9. Epub 2018 Mar 28.
9
Rocaglates as dual-targeting agents for experimental cerebral malaria.
Proc Natl Acad Sci U S A. 2018 Mar 6;115(10):E2366-E2375. doi: 10.1073/pnas.1713000115. Epub 2018 Feb 20.
10
The mouse Char10 locus regulates severity of pyruvate kinase deficiency and susceptibility to malaria.
PLoS One. 2017 May 18;12(5):e0177818. doi: 10.1371/journal.pone.0177818. eCollection 2017.

本文引用的文献

1
Artemisinin resistance in Plasmodium falciparum malaria.
N Engl J Med. 2009 Jul 30;361(5):455-67. doi: 10.1056/NEJMoa0808859.
2
Pyruvate kinase deficiency and malaria.
N Engl J Med. 2008 Apr 24;358(17):1805-10. doi: 10.1056/NEJMoa072464. Epub 2008 Apr 16.
3
Protection against cerebral malaria by the low-molecular-weight thiol pantethine.
Proc Natl Acad Sci U S A. 2008 Jan 29;105(4):1321-6. doi: 10.1073/pnas.0706867105. Epub 2008 Jan 14.
4
Drug-resistant malaria - an insight.
FEBS J. 2007 Sep;274(18):4688-98. doi: 10.1111/j.1742-4658.2007.05999.x.
5
Cellular thiol pools are responsible for sequestration of cytotoxic reactive aldehydes: central role of free cysteine and cysteamine.
Brain Res. 2007 Jul 16;1158:158-63. doi: 10.1016/j.brainres.2007.05.007. Epub 2007 May 10.
6
Complex genetic control of susceptibility to malaria: positional cloning of the Char9 locus.
J Exp Med. 2007 Mar 19;204(3):511-24. doi: 10.1084/jem.20061252. Epub 2007 Feb 20.
7
Vanin-1 controls granuloma formation and macrophage polarization in Coxiella burnetii infection.
Eur J Immunol. 2007 Jan;37(1):24-32. doi: 10.1002/eji.200636054.
9
How malaria has affected the human genome and what human genetics can teach us about malaria.
Am J Hum Genet. 2005 Aug;77(2):171-92. doi: 10.1086/432519. Epub 2005 Jul 6.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验