Peroxisome proliferator-activated receptor γ agonists accelerate oligodendrocyte maturation and influence mitochondrial functions and oscillatory Ca2+ waves
Articolo
Data di Pubblicazione:
2011
Citazione:
Peroxisome proliferator-activated receptor γ agonists accelerate oligodendrocyte maturation and influence mitochondrial functions and oscillatory Ca2+ waves / C. De Nuccio, A. Bernardo, R. De Simone, E. Mancuso, V. Magnaghi, S. Visentin, L. Minghetti. - In: JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY. - ISSN 0022-3069. - 70:10(2011 Oct), pp. 900-912.
Abstract:
We have previously shown that natural (15-deoxy-Δ-prostaglandin J2) and synthetic (pioglitazone) agonists of peroxisome proliferator-activated receptor γ (PPAR-γ) strengthen the intrinsic cellular mechanisms protecting oligodendrocyte (OL) progenitors (OPs) from oxidative insults and promote their differentiation. Here, we demonstrate that repeated administrations of PPAR-γ agonists to OP cultures accelerate their differentiation to OLs, as indicated by increased numbers of O4- and O1-positive cells that show increased myelin basic protein expression, elaborated cholesterol-enrichedmembranes and have increased peroxisomes. Moreover, PPAR-γ agonist-treated OLs show increased activity of the mitochondrial respiratory chain Complex IV and an increased ability to respond to environmental signals, such as adenosine diphosphate (ADP), with oscillatory Ca waves; the latter closely correlated with the presence of mitochondria and were inhibited by the mitochondrial respiratory chain Complex I inhibitor rotenone. Because Ca oscillations and mitochondrial respiratory chain activity play crucial roles in OL differentiation, these findings suggest that PPAR-γ agonists could protect OLs and promote myelination through several mechanisms, including those involving mitochondrial functions. Our studies support the therapeutic potential of PPAR-γ agonists in brain diseases in which mitochondrial alteration, oxidative stress, and demyelination occur and point to the need for a better understanding of the role of PPAR-γ and its agonists in OL biology.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
C. De Nuccio, A. Bernardo, R. De Simone, E. Mancuso, V. Magnaghi, S. Visentin, L. Minghetti
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