A biochemical basis for induction of retina regeneration by antioxidants.
A biochemical basis for induction of retina regeneration by antioxidants.
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DOI：
10.1016/j.ydbio.2017.08.013
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发表时间：
2018-01-15
影响因子：
2.7
通讯作者：
Del Rio-Tsonis K
中科院分区：
文献类型：
--
作者：
Echeverri-Ruiz N;Haynes T;Landers J;Woods J;Gemma MJ;Hughes M;Del Rio-Tsonis K
抗氧化剂在组织再生中的应用已经被研究过，但它们的作用机制还不清楚。在这里，我们分析了抗氧化剂N-乙酰半胱氨酸（NAC）在视网膜再生中的作用。只有当存在外源性因子如FGF 2的来源时，胚胎鸡才能够在从存在于眼睛睫状缘（CM）中的视网膜干细胞/祖细胞中完全去除视网膜后再生它们的视网膜。这项研究表明，NAC修改CM的氧化还原状态，启动干/祖细胞的自我更新，并在没有FGF 2的情况下诱导再生。NAC通过独立地或通过谷胱甘肽（GSH）的合成清除自由基，和/或通过硫醇二硫键交换活性还原氧化蛋白质而作为抗氧化剂起作用。我们剖析了NAC通过使用GSH合成抑制剂和使用具有不同生化结构和作用模式的其他抗氧化剂来诱导再生的机制，发现NAC通过其硫醇二硫键交换活性诱导再生。因此，我们的研究结果首次为诱导视网膜再生提供了生化基础。此外，NAC诱导独立于FGF受体信号，但依赖于MAPK（pErk 1/2）途径。
The use of antioxidants in tissue regeneration has been studied, but their mechanism of action is not well understood. Here, we analyze the role of the antioxidant N-acetylcysteine (NAC) in retina regeneration. Embryonic chicks are able to regenerate their retina after its complete removal from retinal stem/progenitor cells present in the ciliary margin (CM) of the eye only if a source of exogenous factors, such as FGF2, is present. This study shows that NAC modifies the redox status of the CM, initiates self-renewal of the stem/progenitor cells, and induces regeneration in the absence of FGF2. NAC works as an antioxidant by scavenging free radicals either independently or through the synthesis of glutathione (GSH), and/or by reducing oxidized proteins through a thiol disulfide exchange activity. We dissected the mechanism used by NAC to induce regeneration through the use of inhibitors of GSH synthesis and the use of other antioxidants with different biochemical structures and modes of action, and found that NAC induces regeneration through its thiol disulfide exchange activity. Thus, our results provide, for the first time, a biochemical basis for induction of retina regeneration. Furthermore, NAC induction was independent of FGF receptor signaling, but dependent on the MAPK (pErk1/2) pathway.
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影响因子：
46.9
作者：
Lane, Steven W.;Williams, David A.;Watt, Fiona M.
通讯作者：
Watt, Fiona M.
影响因子：
4.8
作者：
Kim, KY;Rhim, T;Kim, SS
通讯作者：
Kim, SS
DOI：
10.1073/pnas.2434516100
发表时间：
2003-12-09
影响因子：
11.1
作者：
Laragione, T;Bonetto, V;Ghezzi, P
通讯作者：
Ghezzi, P
影响因子：
12.4
作者：
Drowley, Lauren;Okada, Masaho;Huard, Johnny
通讯作者：
Huard, Johnny
影响因子：
16.6
作者：
Haynes, Tracy;Luz-Madrigal, Agustin;Reis, Edimara S.;Ruiz, Nancy P. Echeverri;Grajales-Esquivel, Erika;Tzekou, Apostolia;Tsonis, Panagiotis A.;Lambris, John D.;Del Rio-Tsonis, Katia
通讯作者：
Del Rio-Tsonis, Katia