Format

Send to

Choose Destination
Cell Death Differ. 2014 Aug;21(8):1198-208. doi: 10.1038/cdd.2014.35. Epub 2014 Mar 21.

Tumor necrosis factor-α impairs oligodendroglial differentiation through a mitochondria-dependent process.

Author information

1
Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Interdisciplinary Center for the Study of Inflammation (ICSI), Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.
2
1] Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Interdisciplinary Center for the Study of Inflammation (ICSI), Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy [2] Department of Biochemistry, Nencki Institute of Experimental Biology, Warsaw, Poland.
3
Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy.
4
Department of Biochemistry, Nencki Institute of Experimental Biology, Warsaw, Poland.
5
1] Istituto Veneto di Medicina Molecolare, Fondazione per la Ricerca Biomedica Avanzata, Padua, Italy [2] Dipartimento di Scienze Biomediche, Università di Padova, Padua, Italy [3] Consiglio Nazionale delle Ricerche, Istituto di Neuroscienze, Sezione di Padova, Padua, Italy.

Abstract

Mitochondrial defects, affecting parameters such as mitochondrial number and shape, levels of respiratory chain complex components and markers of oxidative stress, have been associated with the appearance and progression of multiple sclerosis. Nevertheless, mitochondrial physiology has never been monitored during oligodendrocyte progenitor cell (OPC) differentiation, especially in OPCs challenged with proinflammatory cytokines. Here, we show that tumor necrosis factor alpha (TNF-α) inhibits OPC differentiation, accompanied by altered mitochondrial calcium uptake, mitochondrial membrane potential, and respiratory complex I activity as well as increased reactive oxygen species production. Treatment with a mitochondrial uncoupler (FCCP) to mimic mitochondrial impairment also causes cells to accumulate at the progenitor stage. Interestingly, AMP-activated protein kinase (AMPK) levels increase during TNF-α exposure and inhibit OPC differentiation. Overall, our data indicate that TNF-α induces metabolic changes, driven by mitochondrial impairment and AMPK activation, leading to the inhibition of OPC differentiation.

PMID:
24658399
PMCID:
PMC4085526
DOI:
10.1038/cdd.2014.35
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center