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 n...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2023-04-01
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| Series: | ASN Neuro |
| Online Access: | https://doi.org/10.1177/17590914231170703 |
| _version_ | 1797840002864906240 |
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| author | María Julia Pérez Tomas Roberto Carden Paula Ayelen dos Santos Claro Susana Silberstein Pablo Martin Páez Veronica Teresita Cheli Jorge Correale Juana M. Pasquini |
| author_facet | María Julia Pérez Tomas Roberto Carden Paula Ayelen dos Santos Claro Susana Silberstein Pablo Martin Páez Veronica Teresita Cheli Jorge Correale Juana M. Pasquini |
| author_sort | María Julia Pérez |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T16:07:19Z |
| format | Article |
| id | doaj.art-4aceba68247e438387501ab492d621a4 |
| institution | Directory Open Access Journal |
| issn | 1759-0914 |
| language | English |
| last_indexed | 2024-04-09T16:07:19Z |
| publishDate | 2023-04-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | ASN Neuro |
| spelling | doaj.art-4aceba68247e438387501ab492d621a42023-04-25T00:33:30ZengSAGE PublishingASN Neuro1759-09142023-04-011510.1177/17590914231170703Transferrin Enhances Neuronal DifferentiationMaría Julia Pérez0Tomas Roberto Carden1Paula Ayelen dos Santos Claro2Susana Silberstein3Pablo Martin Páez4Veronica Teresita Cheli5Jorge Correale6Juana M. Pasquini7 Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina Instituto de Investigación en Biomedicina de Buenos Aires (IBIoBA), CONICET-Partner Institute of The Max Plank Society, Buenos Aires, Argentina Instituto de Investigación en Biomedicina de Buenos Aires (IBIoBA), CONICET-Partner Institute of The Max Plank Society, Buenos Aires, Argentina 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 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 Departamento de Neurología, , Buenos Aires, Argentina Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Universidad de Buenos Aires-CONICET, Buenos Aires, ArgentinaAlthough 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.https://doi.org/10.1177/17590914231170703 |
| spellingShingle | María Julia Pérez Tomas Roberto Carden Paula Ayelen dos Santos Claro Susana Silberstein Pablo Martin Páez Veronica Teresita Cheli Jorge Correale Juana M. Pasquini Transferrin Enhances Neuronal Differentiation ASN Neuro |
| title | Transferrin Enhances Neuronal Differentiation |
| title_full | Transferrin Enhances Neuronal Differentiation |
| title_fullStr | Transferrin Enhances Neuronal Differentiation |
| title_full_unstemmed | Transferrin Enhances Neuronal Differentiation |
| title_short | Transferrin Enhances Neuronal Differentiation |
| title_sort | transferrin enhances neuronal differentiation |
| url | https://doi.org/10.1177/17590914231170703 |
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