Over-Expressing Prohibitin (PHB) in Neuronal Cultures Exacerbates Cell Death Following Hydrogen Peroxide and L-Glutamic Acid Induced Injury
| Autor: | Joanne Chieng, Jonathan Teoh, Bruno P. Meloni, Neville W. Knuckey, Sherif Boulos |
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| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | Neuroscience and Medicine. :149-160 |
| ISSN: | 2158-2947 2158-2912 |
| DOI: | 10.4236/nm.2014.54018 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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