PMID- 24051032
OWN - NLM
STAT- MEDLINE
DCOM- 20140226
LR  - 20140103
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 28
IP  - 1
DP  - 2014 Jan
TI  - Monoamine oxidase-A knockdown in human neuroblastoma cells reveals protection 
      against mitochondrial toxins.
PG  - 218-29
LID - 10.1096/fj.13-235481 [doi]
AB  - The study examined how the mitochondrial enzyme monoamine oxidase-A (MAO-A), 
      which produces hydrogen peroxide as a catalytic by-product, influences death and 
      survival mechanisms. Targeted microRNA (miRNA) was used to stably knock down 
      MAO-A mRNA, protein, and catalytic activity by 60-70% in SH-SY5Y human 
      neuroblastoma cells. The effects of MAO-A knockdown (KD) on ATP, oxidative 
      stress, electron transport chain, and survival following exposure to 
      mitochondrial toxins were assessed. In control cells, complex I inhibition 
      resulted in caspase-mediated cell death linked with ROS production and reduced 
      ATP, followed by up-regulation of MAO-A mRNA, protein, and enzyme activity 
      levels. Inhibition of complex III and IV resulted in a similar increase in MAO-A 
      expression, while up-regulation of MAO-A was lower following complex II 
      inhibition. MAO-A KD decreased basal reactive oxygen species levels by 50% and 
      increased levels of ATP and reduced glutathione and Bcl-2. MAO-A KD specifically 
      increased the activity of complex I but had no effect on complex II-IV 
      activities. Furthermore, MAO-A KD protected against inhibitors of complex I, III, 
      and IV. In summary, endogenous MAO-A levels influence mitochondrial function, 
      notably complex I activity, and MAO-A may be a target for protection against 
      neurodegenerative conditions that involve oxidative stress and mitochondrial 
      dysfunction as underlying pathogenic factors.
FAU - Fitzgerald, Julia C
AU  - Fitzgerald JC
AD  - 2School of Science and Technology, Nottingham Trent University, Nottingham, NG11 
      8NS, UK. ellen.billett@ntu.ac.uk.
FAU - Ugun-Klusek, Aslihan
AU  - Ugun-Klusek A
FAU - Allen, George
AU  - Allen G
FAU - De Girolamo, Luigi A
AU  - De Girolamo LA
FAU - Hargreaves, Iain
AU  - Hargreaves I
FAU - Ufer, Christoph
AU  - Ufer C
FAU - Abramov, Andrey Y
AU  - Abramov AY
FAU - Billett, E Ellen
AU  - Billett EE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130919
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (MicroRNAs)
RN  - 0 (Reactive Oxygen Species)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 1.4.3.4 (Monoamine Oxidase)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Cell Line, Tumor
MH  - Humans
MH  - MicroRNAs/genetics
MH  - Mitochondria/metabolism
MH  - Monoamine Oxidase/genetics/*metabolism
MH  - Neuroblastoma/genetics/*metabolism
MH  - Parkinson Disease/genetics/metabolism
MH  - Reactive Oxygen Species/metabolism
OTO - NOTNLM
OT  - Parkinson's disease
OT  - electron transport chain
OT  - neurodegeneration
OT  - reactive oxygen species
EDAT- 2013/09/21 06:00
MHDA- 2014/02/27 06:00
CRDT- 2013/09/21 06:00
PHST- 2013/09/21 06:00 [entrez]
PHST- 2013/09/21 06:00 [pubmed]
PHST- 2014/02/27 06:00 [medline]
AID - fj.13-235481 [pii]
AID - 10.1096/fj.13-235481 [doi]
PST - ppublish
SO  - FASEB J. 2014 Jan;28(1):218-29. doi: 10.1096/fj.13-235481. Epub 2013 Sep 19.