Rosiglitazone treatment prevents mitochondrial dysfunction in mutant huntingtin-expressing cells -: Possible role of peroxisome proliferator-activated receptor-γ (PPARγ) in the pathogenesis of Huntington disease

Simple item page
dc.contributor.authorQuintanilla, Rodrigo A.
dc.contributor.authorJin, Youngnam N.
dc.contributor.authorFuenzalida, Karen
dc.contributor.authorBronfman, Miguel
dc.contributor.authorJohnson, Gail V. W.
dc.date.accessioned2025-01-21T01:05:00Z
dc.date.available2025-01-21T01:05:00Z
dc.date.issued2008
dc.description.abstractPeroxisome proliferator-activated receptor-gamma (PPAR gamma) is a member of the PPAR family of transcription factors. Synthetic PPAR gamma agonists are used as oral anti-hyperglycemic drugs for the treatment of non-insulin-dependent diabetes. However, emerging evidence indicates that PPAR gamma activators can also prevent or attenuate neurodegeneration. Given these previous findings, the focus of this report is on the potential neuroprotective role of PPAR gamma activation in preventing the loss of mitochondrial function in Huntington disease (HD). For these studies we used striatal cells that express wild-type (STHdh(Q7/Q7)) or mutant (STHdh(Q111/Q111)) huntingtin protein at physiological levels. Treatment of mutant cells with thapsigargin resulted in a significant decrease in mitochondrial calcium uptake, an increase in reactive oxygen species production, and a significant decrease in mitochondrial membrane potential. PPAR gamma activation by rosiglitazone prevented the mitochondrial dysfunction and oxidative stress that occurred when mutant striatal cells were challenged with pathological increases in calcium. The beneficial effects of rosiglitazone were likely mediated by activation of PPAR gamma, as all protective effects were prevented by the PPAR gamma antagonist GW9662. Additionally, the PPAR gamma signaling pathway was significantly impaired in the mutant striatal cells with decreases in PPAR gamma expression and reduced PPAR gamma transcriptional activity. Treatment with rosiglitazone increased mitochondrial mass levels, suggesting a role for the PPAR gamma pathway in mitochondrial function in striatal cells. Altogether, this evidence indicates that PPAR gamma activation by rosiglitazone attenuates mitochondrial dysfunction in mutant huntingtin-expressing striatal cells, and this could be an important therapeutic avenue to ameliorate the mitochondrial dysfunction that occurs in HD.
dc.description.funderNational Institutes of Health
dc.fuente.origenWOS
dc.identifier.doi10.1074/jbc.M804291200
dc.identifier.eissn1083-351X
dc.identifier.issn0021-9258
dc.identifier.urihttps://doi.org/10.1074/jbc.M804291200
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/95773
dc.identifier.wosidWOS:000259012700058
dc.issue.numero37
dc.language.isoen
dc.pagina.final25637
dc.pagina.inicio25628
dc.revistaJournal of biological chemistry
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleRosiglitazone treatment prevents mitochondrial dysfunction in mutant huntingtin-expressing cells -: Possible role of peroxisome proliferator-activated receptor-γ (PPARγ) in the pathogenesis of Huntington disease
dc.typeartículo
dc.volumen283
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
Files
Collections
Artículos de revistas