Author(s)

Jonathan Teoh, Sherif Boulos, Joanne Chieng, Neville W. Knuckey, Bruno P. Meloni

1Centre for Neuromuscular and Neurological Disorders, The University of Western Australia and Western Australian Neuroscience Research Institute, QEII Medical Centre, Nedlands, WA, Australia 2Department of Neurosurgery, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
Centre for Neuromuscular and Neurological Disorders, The University of Western Australia and Western Australian Neuroscience Research Institute, QEII Medical Centre, Nedlands, WA, Australia.

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.

Prohibitin, Neurodamage, Mitochondria, In Vitro Injury Models, Neuronal Cultures

Teoh, J. , Boulos, S. , Chieng, J. , Knuckey, N. and Meloni, B. (2014) Over-Expressing Prohibitin (PHB) in Neuronal Cultures Exacerbates Cell Death Following Hydrogen Peroxide and L-Glutamic Acid Induced Injury. Neuroscience and Medicine, 5, 149-160. doi: 10.4236/nm.2014.54018.