Peroxisome Proliferator-activated Receptor γ Up-regulates the Bcl-2 Anti-apoptotic Protein in Neurons and Induces Mitochondrial Stabilization and Protection against Oxidative Stress and Apoptosis

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dc.contributor.authorFuenzalida, Karen
dc.contributor.authorQuintanilla, Rodrigo
dc.contributor.authorRamos, Patricio
dc.contributor.authorPiderit, Daniela
dc.contributor.authorFuentealba, Rodrigo A.
dc.contributor.authorMartinez, Gabriela
dc.contributor.authorInestrosa, Nibaldo C.
dc.contributor.authorBronfman, Miguel
dc.date.accessioned2024-01-10T12:07:29Z
dc.date.available2024-01-10T12:07:29Z
dc.date.issued2007
dc.description.abstractPeroxisome proliferator-activated receptor gamma(PPAR gamma) has been proposed as a therapeutic target for neurodegenerative diseases because of its anti-inflammatory action in glial cells. However, PPAR gamma agonists prevent beta-amyloid (A beta)-induced neurodegeneration in hippocampal neurons, and PPAR gamma is activated by the nerve growth factor (NGF) survival pathway, suggesting a neuroprotective anti-inflammatory independent action. Here we show that the PPAR gamma agonist rosiglitazone (RGZ) protects hippocampal and dorsal root ganglion neurons against A beta-induced mitochondrial damage and NGF deprivation-induced apoptosis, respectively, and promotes PC12 cell survival. In neurons and in PC12 cells RGZ protective effects are associated with increased expression of the Bcl-2 anti-apoptotic protein. NGF-differentiated PC12 neuronal cells constitutively overexpressing PPAR gamma are resistant to A beta-induced apoptosis and morphological changes and show functionally intact mitochondria and no increase in reactive oxygen species when challenged with up to 50 mu M H2O2. Conversely, cells expressing a dominant negative mutant of PPAR gamma show increased A beta-induced apoptosis and disruption of neuronal-like morphology and are highly sensitive to oxidative stress-induced impairment of mitochondrial function. Cells overexpressing PPAR gamma present a 4-to 5-fold increase in Bcl-2 protein content, whereas in dominant negative PPAR gamma-expressing cells, Bcl-2 is barely detected. Bcl-2 knockdown by small interfering RNA in cells overexpressing PPAR gamma results in increased sensitivity to A beta and oxidative stress, further suggesting that Bcl-2 up-regulation mediates PPAR gamma protective effects. PPAR gamma prosurvival action is independent of the signal-regulated MAPK or the Akt prosurvival pathways. Altogether, these data suggest that PPAR gamma supports survival in neurons in part through a mechanism involving increased expression of Bcl-2.
dc.fechaingreso.objetodigital2024-04-25
dc.format.extent10 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1074/jbc.M700447200
dc.identifier.eissn1083-351X
dc.identifier.issn0021-9258
dc.identifier.pubmedidMEDLINE:17965419
dc.identifier.urihttps://doi.org/10.1074/jbc.M700447200
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/76289
dc.identifier.wosidWOS:000251646000027
dc.information.autorucCiencias Biológicas;Bronfman M;S/I;98819
dc.information.autorucCiencias Biológicas;Inestrosa NC;S/I;99331
dc.issue.numero51
dc.language.isoen
dc.nota.accesocontenido completo
dc.pagina.final37015
dc.pagina.inicio37006
dc.publisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
dc.revistaJOURNAL OF BIOLOGICAL CHEMISTRY
dc.rightsacceso abierto
dc.subjectNERVE GROWTH-FACTOR
dc.subjectPPAR-GAMMA
dc.subjectCELL-DEATH
dc.subjectALZHEIMERS-DISEASE
dc.subjectINSULIN-RESISTANCE
dc.subjectSIGNALING PATHWAY
dc.subjectSURVIVAL
dc.subjectAGONISTS
dc.subjectTROGLITAZONE
dc.subjectLIGAND
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titlePeroxisome Proliferator-activated Receptor γ Up-regulates the Bcl-2 Anti-apoptotic Protein in Neurons and Induces Mitochondrial Stabilization and Protection against Oxidative Stress and Apoptosis
dc.typeartículo
dc.volumen282
sipa.codpersvinculados98819
sipa.codpersvinculados99331
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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