St Andrews Research Repository

St Andrews University Home
View Item 
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  • Login
JavaScript is disabled for your browser. Some features of this site may not work without it.

Delta-9-tetrahydrocannabinol protects against MPP+ toxicity in SH-SY5Y cells by restoring proteins involved in mitochondrial biogenesis

Thumbnail
View/Open
Zajicek_2016_Oncotarget_SH_SY5YCells_CC.pdf (2.111Mb)
Date
27/06/2016
Author
Zeissler, Marie-Louise
Eastwood, Jordan
McCorry, Kieran
Hanemann, C. Oliver
Zajicek, John P.
Carroll, Camille B.
Keywords
Mitochondrial biogenesis
MPP+
Parkinson's disease
Peroxisome proliferator-activated receptor
Δ9-tetrahydrocannabinol
RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Oncology
NDAS
Metadata
Show full item record
Altmetrics Handle Statistics
Altmetrics DOI Statistics
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 1a (PGC-1a), 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.
Citation
Zeissler , M-L , Eastwood , J , McCorry , K , Hanemann , C O , Zajicek , J P & Carroll , C B 2016 , ' Delta-9-tetrahydrocannabinol protects against MPP + toxicity in SH-SY5Y cells by restoring proteins involved in mitochondrial biogenesis ' , Oncotarget , vol. 7 , no. 29 , pp. 46603-46614 . https://doi.org/10.18632/oncotarget.10314
Publication
Oncotarget
Status
Peer reviewed
DOI
https://doi.org/10.18632/oncotarget.10314
ISSN
1949-2553
Type
Journal article
Rights
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
Description
This project was supported through a studentship awarded by the Plymouth University Peninsula Schools of Medicine and Dentistry.
Collections
  • University of St Andrews Research
URL
http://www.scopus.com/inward/record.url?scp=84979895378&partnerID=8YFLogxK
URI
http://hdl.handle.net/10023/9313

Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.

Advanced Search

Browse

All of RepositoryCommunities & CollectionsBy Issue DateNamesTitlesSubjectsClassificationTypeFunderThis CollectionBy Issue DateNamesTitlesSubjectsClassificationTypeFunder

My Account

Login

Open Access

To find out how you can benefit from open access to research, see our library web pages and Open Access blog. For open access help contact: openaccess@st-andrews.ac.uk.

Accessibility

Read our Accessibility statement.

How to submit research papers

The full text of research papers can be submitted to the repository via Pure, the University's research information system. For help see our guide: How to deposit in Pure.

Electronic thesis deposit

Help with deposit.

Repository help

For repository help contact: Digital-Repository@st-andrews.ac.uk.

Give Feedback

Cookie policy

This site may use cookies. Please see Terms and Conditions.

Usage statistics

COUNTER-compliant statistics on downloads from the repository are available from the IRUS-UK Service. Contact us for information.

© University of St Andrews Library

University of St Andrews is a charity registered in Scotland, No SC013532.

  • Facebook
  • Twitter