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DOI | 10.1111/jnc.14015 |
The viral protein gp120 decreases the acetylation of neuronal tubulin: potential mechanism of neurotoxicity | |
Avdoshina, Valeria1,3; Caragher, Seamus P.1,3; Wenzel, Erin D.1,2,3,4; Taraballi, Francesca5; Mocchetti, Italo1,3; Harry, Gaylia Jean6 | |
发表日期 | 2017-05-01 |
ISSN | 0022-3042 |
卷号 | 141期号:4页码:606-613 |
英文摘要 | The human immunodeficiency virus (HIV) envelope protein gp120 promotes axonal damage and neurite pruning, similar to that observed in HIV-positive subjects with neurocognitive disorders. Thus, gp120 has been used to examine molecular and cellular pathways underlying HIV-mediated neuronal dysfunction. Gp120 binds to tubulin beta III, a component of neuronal microtubules. Microtubule function, which modulates the homeostasis of neurons, is regulated by polymerization and post-translational modifications. Based on these considerations, we tested the hypothesis that gp120 induces dynamic instability of neuronal microtubules. We first observed that gp120 prevents the normal polymerization of tubulin invitro. We then tested whether gp120 alters the post-translational modifications in tubulin by examining the ability of gp120 to change the levels of acetylated tubulin in primary rat neuronal cultures. Gp120 elicited a time-dependent decrease in tubulin acetylation that was reversed by Helix-A peptide, a compound that competitively displaces the binding of gp120 to neuronal microtubules. To determine whether post-translational modifications in tubulin also occur invivo, we measured acetylated tubulin in the cerebral cortex of HIV transgenic rats (HIV-tg). We observed a decrease in tubulin acetylation in 5- and 9-month-old HIV-tg rats when compared to age-matched wild type. Neither changes in microglia morphology nor alterations in mRNA levels for interleukin-1 beta and tumor necrosis factor were detected in 5-month-old animals. Our findings propose neuronal microtubule instability as a novel mechanism of HIV neurotoxicity, without evidence of enhanced inflammation. |
英文关键词 | HAND;Helix-A peptide;HIV transgenic rats;microglia;microtubules |
语种 | 英语 |
WOS记录号 | WOS:000400692200012 |
来源期刊 | JOURNAL OF NEUROCHEMISTRY |
来源机构 | 美国环保署 |
文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/60557 |
作者单位 | 1.Georgetown Univ, Lab Preclin Neurobiol Dept Neuroscience, Washington, DE USA; 2.Georgetown Univ, Dept Physiol & Pharmacol, Washington, DE USA; 3.Georgetown Univ, Dept Neurosci, Lab Preclin Neurobiol, Washington, DC USA; 4.Georgetown Univ, Dept Physiol & Pharmacol, Georgetown, Guyana; 5.Houston Methodist Res Inst, Dept Regenerat Med, Houston, TX USA; 6.Natl Inst Environm Hlth Sci, Natl Toxicol Program Lab, Res Triangle Pk, NC USA |
推荐引用方式 GB/T 7714 | Avdoshina, Valeria,Caragher, Seamus P.,Wenzel, Erin D.,et al. The viral protein gp120 decreases the acetylation of neuronal tubulin: potential mechanism of neurotoxicity[J]. 美国环保署,2017,141(4):606-613. |
APA | Avdoshina, Valeria,Caragher, Seamus P.,Wenzel, Erin D.,Taraballi, Francesca,Mocchetti, Italo,&Harry, Gaylia Jean.(2017).The viral protein gp120 decreases the acetylation of neuronal tubulin: potential mechanism of neurotoxicity.JOURNAL OF NEUROCHEMISTRY,141(4),606-613. |
MLA | Avdoshina, Valeria,et al."The viral protein gp120 decreases the acetylation of neuronal tubulin: potential mechanism of neurotoxicity".JOURNAL OF NEUROCHEMISTRY 141.4(2017):606-613. |
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