Brain-Derived Neurotrophic Factor Inhibits Phenylalanine-Induced Neuronal Apoptosis by Preventing RhoA Pathway Activation
| Autor: | Yongjun Zhang, Jing Wang, Jing Zhao, Xianting Jiao |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Myosin Light Chains
RHOA Phenylalanine Blotting Western Apoptosis Tropomyosin receptor kinase B Biochemistry Neuroprotection GTP Phosphohydrolases Rats Sprague-Dawley Cellular and Molecular Neuroscience chemistry.chemical_compound Cytosol Downregulation and upregulation In Situ Nick-End Labeling Animals Receptor trkB Phosphorylation Biotransformation Cells Cultured Neurons Brain-derived neurotrophic factor biology Brain-Derived Neurotrophic Factor General Medicine Mitochondria Rats Cell biology nervous system chemistry Trk receptor Cancer research biology.protein RNA Interference K252a Signal transduction rhoA GTP-Binding Protein Signal Transduction |
| Zdroj: | Neurochemical Research. 35:480-486 |
| ISSN: | 1573-6903 0364-3190 |
| Popis: | Phenylketonuria (PKU) is neuropathologically characterized by neuronal cell loss, white matter abnormalities, dendritic simplification, and synaptic density reduction. The neuropathological effect may be due to the 'toxicity' of the high concentration of phenylalanine, while little is known about the related treatments to block this effect. In this study, we reported that brain-derived growth factor (BDNF) protected neurons from phenylalanine-induced apoptosis and inhibition of Trk receptor by K252a or downregulation of TrkB abrogated the effect of BDNF. We further demonstrated that phenylalanine-induced RhoA activation and myosin light chain phosphorylation were inhibited by pretreatment with BDNF, while phenylalanine activates the mitochondria-mediated apoptosis through the RhoA/Rho-associated kinase pathway. Thus our studies indicate that the protective effect of BDNF against phenylalanine-induced neuronal apoptosis is probably mediated by suppression of RhoA signaling pathway via TrkB receptor. Taken together, these findings suggest a potential neuroprotective action of BDNF in prevention and treatment of PKU brain injury. |
| Databáze: | OpenAIRE |
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