A role for hemopexin in oligodendrocyte differentiation and myelin formation.
Myelin formation and maintenance are crucial for the proper function of the CNS and are orchestrated by a plethora of factors including growth factors, extracellular matrix components, metalloproteases and protease inhibitors. Hemopexin (Hx) is a plasma protein with high heme binding affinity, which...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3102107?pdf=render |
| _version_ | 1818855136970145792 |
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| author | Noemi Morello Federico Tommaso Bianchi Paola Marmiroli Elisabetta Tonoli Virginia Rodriguez Menendez Lorenzo Silengo Guido Cavaletti Alessandro Vercelli Fiorella Altruda Emanuela Tolosano |
| author_facet | Noemi Morello Federico Tommaso Bianchi Paola Marmiroli Elisabetta Tonoli Virginia Rodriguez Menendez Lorenzo Silengo Guido Cavaletti Alessandro Vercelli Fiorella Altruda Emanuela Tolosano |
| author_sort | Noemi Morello |
| collection | DOAJ |
| description | Myelin formation and maintenance are crucial for the proper function of the CNS and are orchestrated by a plethora of factors including growth factors, extracellular matrix components, metalloproteases and protease inhibitors. Hemopexin (Hx) is a plasma protein with high heme binding affinity, which is also locally produced in the CNS by ependymal cells, neurons and glial cells. We have recently reported that oligodendrocytes (OLs) are the type of cells in the brain that are most susceptible to lack of Hx, as the number of iron-overloaded OLs increases in Hx-null brain, leading to oxidative tissue damage. In the current study, we found that the expression of the Myelin Basic Protein along with the density of myelinated fibers in the basal ganglia and in the motor and somatosensory cortex of Hx-null mice were strongly reduced starting at 2 months and progressively decreased with age. Myelin abnormalities were confirmed by electron microscopy and, at the functional level, resulted in the inability of Hx-null mice to perform efficiently on the Rotarod. It is likely that the poor myelination in the brain of Hx-null mice was a consequence of defective maturation of OLs as we demonstrated that the number of mature OLs was significantly reduced in mutant mice whereas that of precursor cells was normal. Finally, in vitro experiments showed that Hx promotes OL differentiation. Thus, Hx may be considered a novel OL differentiation factor and the modulation of its expression in CNS may be an important factor in the pathogenesis of human neurodegenerative disorders. |
| first_indexed | 2024-12-19T08:03:49Z |
| format | Article |
| id | doaj.art-64736b266a804ffba023a781e7d76a95 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T08:03:49Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-64736b266a804ffba023a781e7d76a952022-12-21T20:29:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0165e2017310.1371/journal.pone.0020173A role for hemopexin in oligodendrocyte differentiation and myelin formation.Noemi MorelloFederico Tommaso BianchiPaola MarmiroliElisabetta TonoliVirginia Rodriguez MenendezLorenzo SilengoGuido CavalettiAlessandro VercelliFiorella AltrudaEmanuela TolosanoMyelin formation and maintenance are crucial for the proper function of the CNS and are orchestrated by a plethora of factors including growth factors, extracellular matrix components, metalloproteases and protease inhibitors. Hemopexin (Hx) is a plasma protein with high heme binding affinity, which is also locally produced in the CNS by ependymal cells, neurons and glial cells. We have recently reported that oligodendrocytes (OLs) are the type of cells in the brain that are most susceptible to lack of Hx, as the number of iron-overloaded OLs increases in Hx-null brain, leading to oxidative tissue damage. In the current study, we found that the expression of the Myelin Basic Protein along with the density of myelinated fibers in the basal ganglia and in the motor and somatosensory cortex of Hx-null mice were strongly reduced starting at 2 months and progressively decreased with age. Myelin abnormalities were confirmed by electron microscopy and, at the functional level, resulted in the inability of Hx-null mice to perform efficiently on the Rotarod. It is likely that the poor myelination in the brain of Hx-null mice was a consequence of defective maturation of OLs as we demonstrated that the number of mature OLs was significantly reduced in mutant mice whereas that of precursor cells was normal. Finally, in vitro experiments showed that Hx promotes OL differentiation. Thus, Hx may be considered a novel OL differentiation factor and the modulation of its expression in CNS may be an important factor in the pathogenesis of human neurodegenerative disorders.http://europepmc.org/articles/PMC3102107?pdf=render |
| spellingShingle | Noemi Morello Federico Tommaso Bianchi Paola Marmiroli Elisabetta Tonoli Virginia Rodriguez Menendez Lorenzo Silengo Guido Cavaletti Alessandro Vercelli Fiorella Altruda Emanuela Tolosano A role for hemopexin in oligodendrocyte differentiation and myelin formation. PLoS ONE |
| title | A role for hemopexin in oligodendrocyte differentiation and myelin formation. |
| title_full | A role for hemopexin in oligodendrocyte differentiation and myelin formation. |
| title_fullStr | A role for hemopexin in oligodendrocyte differentiation and myelin formation. |
| title_full_unstemmed | A role for hemopexin in oligodendrocyte differentiation and myelin formation. |
| title_short | A role for hemopexin in oligodendrocyte differentiation and myelin formation. |
| title_sort | role for hemopexin in oligodendrocyte differentiation and myelin formation |
| url | http://europepmc.org/articles/PMC3102107?pdf=render |
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