| Autor: |
Pérez MJ; Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.; Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina., Carden TR; Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.; Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina., Dos Santos Claro PA; Instituto de Investigación en Biomedicina de Buenos Aires (IBIoBA), CONICET-Partner Institute of The Max Plank Society, Buenos Aires, Argentina., Silberstein S; Instituto de Investigación en Biomedicina de Buenos Aires (IBIoBA), CONICET-Partner Institute of The Max Plank Society, Buenos Aires, Argentina., Páez PM; Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, Institute for Myelin and Glia Exploration, State University of New York at Buffalo, Buffalo, New York, USA., Cheli VT; Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, Institute for Myelin and Glia Exploration, State University of New York at Buffalo, Buffalo, New York, USA., Correale J; Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.; Departamento de Neurología, Fleni, Buenos Aires, Argentina., Pasquini JM; Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.; Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina. |
| Abstrakt: |
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. |
