转铁蛋白促进神经元分化。

IF 3.9 4区 医学 Q2 NEUROSCIENCES ASN NEURO Pub Date : 2023-01-01 DOI:10.1177/17590914231170703
María Julia Pérez, Tomas Roberto Carden, Paula Ayelen Dos Santos Claro, Susana Silberstein, Pablo Martin Páez, Veronica Teresita Cheli, Jorge Correale, Juana M Pasquini
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摘要

虽然转铁蛋白(Tf)是一种糖蛋白,以其在铁传递中的作用而闻名,但也有报道称其具有不依赖铁的功能。在这里,我们评估了apoTf (aTf)对神经-2a (N2a)细胞的治疗效果,神经-2a是一种小鼠神经母细胞瘤细胞系,一旦分化,与神经元共享许多特性,包括过程产物、选择性神经元标记物的表达和电活动。我们首先在我们的模型中检测了Tf与其受体(TfR)的结合,并验证了N2a细胞像神经元一样可以从培养基中内化Tf。接下来,对神经元发育参数的研究表明,Tf通过减少细胞凋亡来提高N2a的存活率。此外,Tf通过促进神经突的生长来加速N2a细胞的形态发育。在aTf处理的小鼠皮质神经元原代培养物中也观察到这些促进分化的作用,因为神经元的成熟速度高于对照组,并且早期神经元标记物的表达减少。在富铁和缺铁培养基中进行的进一步实验表明,Tf在N2a细胞中保持了其促分化特性,结果提示铁的调节作用。此外,N2a-小胶质细胞共培养显示,aTf处理后IL-10增加,这可能被认为有利于N2a分化。综上所述,这些发现表明Tf可以减少细胞死亡并促进神经元分化过程,因此使Tf成为一个有希望用于神经退行性疾病的再生策略的候选者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Transferrin Enhances Neuronal Differentiation.

Although transferrin (Tf) is a glycoprotein best known for its role in iron delivery, iron-independent functions have also been reported. Here, we assessed apoTf (aTf) treatment effects on Neuro-2a (N2a) cells, a mouse neuroblastoma cell line which, once differentiated, shares many properties with neurons, including process outgrowth, expression of selective neuronal markers, and electrical activity. We first examined the binding of Tf to its receptor (TfR) in our model and verified that, like neurons, N2a cells can internalize Tf from the culture medium. Next, studies on neuronal developmental parameters showed that Tf increases N2a survival through a decrease in apoptosis. Additionally, Tf accelerated the morphological development of N2a cells by promoting neurite outgrowth. These pro-differentiating effects were also observed in primary cultures of mouse cortical neurons treated with aTf, as neurons matured at a higher rate than controls and showed a decrease in the expression of early neuronal markers. Further experiments in iron-enriched and iron-deficient media showed that Tf preserved its pro-differentiation properties in N2a cells, with results hinting at a modulatory role for iron. Moreover, N2a-microglia co-cultures revealed an increase in IL-10 upon aTf treatment, which may be thought to favor N2a differentiation. Taken together, these findings suggest that Tf reduces cell death and favors the neuronal differentiation process, thus making Tf a promising candidate to be used in regenerative strategies for neurodegenerative diseases.

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来源期刊
ASN NEURO
ASN NEURO NEUROSCIENCES-
CiteScore
7.70
自引率
4.30%
发文量
35
审稿时长
>12 weeks
期刊介绍: ASN NEURO is an open access, peer-reviewed journal uniquely positioned to provide investigators with the most recent advances across the breadth of the cellular and molecular neurosciences. The official journal of the American Society for Neurochemistry, ASN NEURO is dedicated to the promotion, support, and facilitation of communication among cellular and molecular neuroscientists of all specializations.
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