PMID- 23675519
OWN - NLM
STAT- MEDLINE
DCOM- 20131209
LR  - 20231106
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 5
DP  - 2013
TI  - Peroxisome proliferator-activated receptor (PPAR) gamma and PPARalpha agonists modulate 
      mitochondrial fusion-fission dynamics: relevance to reactive oxygen species 
      (ROS)-related neurodegenerative disorders?
PG  - e64019
LID - 10.1371/journal.pone.0064019 [doi]
LID - e64019
AB  - Recent studies showed that the activation of the retinoid X receptor, which 
      dimerizes with peroxisome proliferator-activated receptors (PPARs), leads to an 
      enhanced clearance of Abeta from the brain of transgenic mice model of Alzheimer's 
      disease (AD), because an increased expression of apolipoprotein E and it main 
      transporters. However, the effects observed must involve additional underlying 
      mechanisms that have not been yet explored. Several studies conducted in our 
      laboratory suggest that part of the effects observed for the PPARs agonist might 
      involves mitochondrial function and, particularly, mitochondrial dynamics. In the 
      present study we assessed the effects of oxidative stress challenge on 
      mitochondrial morphology and mitochondrial dynamics-related proteins in 
      hippocampal neurons. Using immunofluorescence, we evaluated the PPARgamma 
      co-activator 1alpha (PGC-1alpha), dynamin related protein 1 (DRP1), mitochondrial fission 
      protein 1 (FIS1), and mitochondrial length, in order to determine if PPARs 
      agonist pre-treatment is able to protect mitochondrial population from 
      hippocampal neurons through modulation of the mitochondrial fusion-fission 
      events. Our results suggest that both a PPARgamma agonist (ciglitazone) and a PPARalpha 
      agonist (WY 14.643) are able to protect neurons by modulating mitochondrial 
      fusion and fission, leading to a better response of neurons to oxidative stress, 
      suggesting that a PPAR based therapy could acts simultaneously in different 
      cellular components. Additionally, our results suggest that PGC-1alpha and 
      mitochondrial dynamics should be further studied in future therapy research 
      oriented to ameliorate neurodegenerative disorders, such as AD.
FAU - Zolezzi, Juan M
AU  - Zolezzi JM
AD  - Departamento de Biologia, Facultad de Ciencias, Universidad de Tarapaca, Arica, 
      Chile.
FAU - Silva-Alvarez, Carmen
AU  - Silva-Alvarez C
FAU - Ordenes, Daniela
AU  - Ordenes D
FAU - Godoy, Juan A
AU  - Godoy JA
FAU - Carvajal, Francisco J
AU  - Carvajal FJ
FAU - Santos, Manuel J
AU  - Santos MJ
FAU - Inestrosa, Nibaldo C
AU  - Inestrosa NC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130513
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Fis1 protein, rat)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (PPAR alpha)
RN  - 0 (PPAR gamma)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, rat)
RN  - 0 (Pyrimidines)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Transcription Factors)
RN  - 86C4MRT55A (pirinixic acid)
RN  - EC 3.6.5.5 (Dnm1l protein, rat)
RN  - EC 3.6.5.5 (Dynamins)
RN  - U8QXS1WU8G (ciglitazone)
SB  - IM
MH  - Animals
MH  - Dynamins/genetics/metabolism
MH  - Embryo, Mammalian
MH  - Gene Expression Regulation
MH  - Hippocampus/cytology/drug effects/metabolism
MH  - Mitochondria/*drug effects/genetics/metabolism/ultrastructure
MH  - Mitochondrial Dynamics/*drug effects/genetics
MH  - Mitochondrial Proteins/genetics/metabolism
MH  - Neurons/cytology/drug effects/metabolism
MH  - Oxidative Stress
MH  - PPAR alpha/*agonists/genetics/metabolism
MH  - PPAR gamma/*agonists/genetics/metabolism
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
MH  - Primary Cell Culture
MH  - Pyrimidines/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
MH  - Thiazolidinediones/*pharmacology
MH  - Transcription Factors/genetics/metabolism
PMC - PMC3652852
COIS- Competing Interests: The authors have declared that no competing interests 
      exists.
EDAT- 2013/05/16 06:00
MHDA- 2013/12/16 06:00
PMCR- 2013/05/13
CRDT- 2013/05/16 06:00
PHST- 2013/02/07 00:00 [received]
PHST- 2013/04/09 00:00 [accepted]
PHST- 2013/05/16 06:00 [entrez]
PHST- 2013/05/16 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
PHST- 2013/05/13 00:00 [pmc-release]
AID - PONE-D-13-06880 [pii]
AID - 10.1371/journal.pone.0064019 [doi]
PST - epublish
SO  - PLoS One. 2013 May 13;8(5):e64019. doi: 10.1371/journal.pone.0064019. Print 2013.