Delta-9-tetrahydrocannabinol protects against MPP+ toxicity in SH-SY5Y cells by restoring proteins involved in mitochondrial biogenesis
dc.contributor.author | Zeissler, M-L | |
dc.contributor.author | Eastwood, J | |
dc.contributor.author | McCorry, K | |
dc.contributor.author | Hanemann, Clemens Oliver | |
dc.contributor.author | Zajicek, JP | |
dc.contributor.author | Carroll, Camille | |
dc.date.accessioned | 2016-07-06T17:35:10Z | |
dc.date.accessioned | 2016-07-06T17:39:33Z | |
dc.date.available | 2016-07-06T17:35:10Z | |
dc.date.available | 2016-07-06T17:39:33Z | |
dc.date.issued | 2016-06-27 | |
dc.identifier.issn | 1949-2553 | |
dc.identifier.issn | 1949-2553 | |
dc.identifier.uri | http://hdl.handle.net/10026.1/5027 | |
dc.description.abstract |
Proliferator-activated receptor γ (PPARγ) activation can result in transcription of proteins involved in oxidative stress defence and mitochondrial biogenesis which could rescue mitochondrial dysfunction in Parkinson's disease (PD).The PPARγ agonist pioglitazone is protective in models of PD; however side effects have limited its clinical use. The cannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) may have PPARγ dependent anti-oxidant properties. Here we investigate the effects of Δ9-THC and pioglitazone on mitochondrial biogenesis and oxidative stress. Differentiated SH-SY5Y neuroblastoma cells were exposed to the PD relevant mitochondrial complex 1 inhibitor 1-methyl-4-phenylpyridinium iodide (MPP+). We found that only Δ9-THC was able to restore mitochondrial content in MPP+ treated SH-SY5Y cells in a PPARγ dependent manner by increasing expression of the PPARγ co-activator 1α (PGC-1α), the mitochondrial transcription factor (TFAM) as well as mitochondrial DNA content. Co-application of Δ9-THC with pioglitazone further increased the neuroprotection against MPP+ toxicity as compared to pioglitazone treatment alone. Furthermore, using lentiviral knock down of the PPARγ receptor we showed that, unlike pioglitazone, Δ9-THC resulted in a PPARγ dependent reduction of MPP+ induced oxidative stress. We therefore suggest that, in contrast to pioglitazone, Δ9-THC mediates neuroprotection via PPARγ-dependent restoration of mitochondrial content which may be beneficial for PD treatment. | |
dc.format.extent | 46603-46614 | |
dc.format.medium | ||
dc.language | en | |
dc.language.iso | en | |
dc.publisher | Impact Journals, LLC | |
dc.relation.replaces | http://hdl.handle.net/10026.1/5026 | |
dc.relation.replaces | 10026.1/5026 | |
dc.subject | Delta(9)-tetrahydrocannabinol | |
dc.subject | peroxisome proliferator-activated receptor | |
dc.subject | MPP+ | |
dc.subject | mitochondrial biogenesis | |
dc.subject | Parkinson's disease | |
dc.title | Delta-9-tetrahydrocannabinol protects against MPP+ toxicity in SH-SY5Y cells by restoring proteins involved in mitochondrial biogenesis | |
dc.type | journal-article | |
dc.type | Journal Article | |
plymouth.author-url | https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000385402300134&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008 | |
plymouth.issue | 29 | |
plymouth.volume | 7 | |
plymouth.publication-status | Accepted | |
plymouth.journal | Oncotarget | |
dc.identifier.doi | 10.18632/oncotarget.10314 | |
plymouth.organisational-group | /Plymouth | |
plymouth.organisational-group | /Plymouth/Faculty of Health | |
plymouth.organisational-group | /Plymouth/Faculty of Health/Peninsula Medical School | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA/UoA03 Allied Health Professions, Dentistry, Nursing and Pharmacy | |
plymouth.organisational-group | /Plymouth/Research Groups | |
plymouth.organisational-group | /Plymouth/Research Groups/FoH - Applied Parkinson's Research | |
plymouth.organisational-group | /Plymouth/Research Groups/FoH - Community and Primary Care | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED) | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CCT&PS | |
plymouth.organisational-group | /Plymouth/Research Groups/Plymouth Institute of Health and Care Research (PIHR) | |
plymouth.organisational-group | /Plymouth/Users by role | |
plymouth.organisational-group | /Plymouth/Users by role/Academics | |
plymouth.organisational-group | /Plymouth/Users by role/Researchers in ResearchFish submission | |
dc.publisher.place | United States | |
dcterms.dateAccepted | 2016-05-09 | |
dc.identifier.eissn | 1949-2553 | |
dc.rights.embargoperiod | No embargo | |
rioxxterms.funder | Medical Research Council | |
rioxxterms.identifier.project | Molecular genetic studies of iron metabolism in Parkinson's disease and related neurodegenerative disorders | |
rioxxterms.versionofrecord | 10.18632/oncotarget.10314 | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2016-06-27 | |
rioxxterms.type | Journal Article/Review | |
plymouth.funder | Molecular genetic studies of iron metabolism in Parkinson's disease and related neurodegenerative disorders::Medical Research Council |