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Accetta R, Damiano S, Morano A, et al. Reactive Oxygen Species Derived from NOX3 and NOX5 Drive Differentiation of Human Oligodendrocytes. Front Cell Neurosci. 2016;10:146doi: 10.3389/fncel.2016.00146.
Accetta, R., Damiano, S., Morano, A., Mondola, P., Paternò, R., Avvedimento, E. V., & Santillo, M. (2016). Reactive Oxygen Species Derived from NOX3 and NOX5 Drive Differentiation of Human Oligodendrocytes. Frontiers in cellular neuroscience, 10146. https://doi.org/10.3389/fncel.2016.00146
Accetta, Roberta, et al. "Reactive Oxygen Species Derived from NOX3 and NOX5 Drive Differentiation of Human Oligodendrocytes." Frontiers in cellular neuroscience vol. 10 (2016): 146. doi: https://doi.org/10.3389/fncel.2016.00146
Accetta R, Damiano S, Morano A, Mondola P, Paternò R, Avvedimento EV, Santillo M. Reactive Oxygen Species Derived from NOX3 and NOX5 Drive Differentiation of Human Oligodendrocytes. Front Cell Neurosci. 2016 Jun 02;10:146. doi: 10.3389/fncel.2016.00146. eCollection 2016. PMID: 27313511; PMCID: PMC4889614.
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Front Cell Neurosci. 2016 Jun 02;10:146. doi: 10.3389/fncel.2016.00146. eCollection 2016.

Reactive Oxygen Species Derived from NOX3 and NOX5 Drive Differentiation of Human Oligodendrocytes.

Frontiers in cellular neuroscience

Roberta Accetta, Simona Damiano, Annalisa Morano, Paolo Mondola, Roberto Paternò, Enrico V Avvedimento, Mariarosaria Santillo

Affiliations

  1. Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli Federico II Naples, Italy.
  2. Laboratori di Ricerca Preclinica e Traslazionale, Istituto di Ricovero e Cura a Carattere Scientifico - Centro di Riferimento Oncologico della Basilicata Rionero in Vulture, Italy.
  3. Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II Naples, Italy.

PMID: 27313511 PMCID: PMC4889614 DOI: 10.3389/fncel.2016.00146

Abstract

Reactive oxygen species (ROS) are signaling molecules that mediate stress response, apoptosis, DNA damage, gene expression and differentiation. We report here that differentiation of oligodendrocytes (OLs), the myelin forming cells in the CNS, is driven by ROS. To dissect the OL differentiation pathway, we used the cell line MO3-13, which display the molecular and cellular features of OL precursors. These cells exposed 1-4 days to low levels of H2O2 or to the protein kinase C (PKC) activator, phorbol-12-Myristate-13-Acetate (PMA) increased the expression of specific OL differentiation markers: the specific nuclear factor Olig-2, and Myelin Basic Protein (MBP), which was processed and accumulated selectively in membranes. The induction of differentiation genes was associated with the activation of ERK1-2 and phosphorylation of the nuclear cAMP responsive element binding protein 1 (CREB). PKC mediates ROS-induced differentiation because PKC depletion or bis-indolyl-maleimide (BIM), a PKC inhibitor, reversed the induction of differentiation markers by H2O2. H2O2 and PMA increased the expression of membrane-bound NADPH oxidases, NOX3 and NOX5. Selective depletion of these proteins inhibited differentiation induced by PMA. Furthermore, NOX5 silencing down regulated NOX3 mRNA levels, suggesting that ROS produced by NOX5 up-regulate NOX3 expression. These data unravel an elaborate network of ROS-generating enzymes (NOX5 to NOX3) activated by PKC and necessary for differentiation of OLs. Furthermore, NOX3 and NOX5, as inducers of OL differentiation, represent novel targets for therapies of demyelinating diseases, including multiple sclerosis, associated with impairment of OL differentiation.

Keywords: NOX3; NOX5; differentiation; multiple sclerosis; oligodendrocyte; reactive oxygen species

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