TITLE:
Over-Expressing Prohibitin (PHB) in Neuronal Cultures Exacerbates Cell Death Following Hydrogen Peroxide and L-Glutamic Acid Induced Injury
AUTHORS:
Jonathan Teoh, Sherif Boulos, Joanne Chieng, Neville W. Knuckey, Bruno P. Meloni
KEYWORDS:
Prohibitin, Neurodamage, Mitochondria, In Vitro Injury Models, Neuronal Cultures
JOURNAL NAME:
Neuroscience and Medicine,
Vol.5 No.4,
September
1,
2014
ABSTRACT: Using proteomics, previous work in our
laboratory identified five mitochondrial related proteins [citrate synthase (CS), glucose-regulated protein 75 (GRP75), heat
shock protein 60 (HSP60), prohibitin (PHB), voltage-dependent anion channel 1
(VDAC1)] to be
differentially expressed in primary cortical neuronal cultures following
preconditioning treatments[1] [2]. To investigate a protective or damaging
role of these five proteins in neurons, we used RNAi constructs to knockdown
and adenoviral vectors to over-express the proteins in cortical neuronal
cultures prior to exposure to three
ischemia-related injury models: excitotoxicity (L-glutamic acid), oxidative stress
(hydrogen peroxide) and in vitro ischemia (oxygen-glucose deprivation). We observed
that down-regulating
these mitochondrial proteins had no effect on neuronal viability, in any injury
model. By contrast, over-expression of PHB
exacerbated cell death in the hydrogen peroxide and L-glutamic acid injury
models. These findings indicate that PHB plays a neurodamaging role following
oxidative and excitotoxic stress and suggests that the protein is a potential therapeutic
target for the design of drugs to limit neuronal death following cerebral ischemia
and other forms of brain injury.