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Interactions between SIRT1 and MAPK/ERK regulate neuronal apoptosis induced by traumatic brain injury in vitro and in vivo
| Content Provider | Semantic Scholar |
|---|---|
| Author | Zhao, Yongbo Luo, Peng Guo, Qindong Li, San-Zhong Fei, Zhou |
| Copyright Year | 2012 |
| Abstract | Traumatic brain injury (TBI) is a serious insult that frequently leads to neurological dysfunction or death. Silent information regulator family protein 1 (SIRT1), as the founding member of nicotinamide adenine dinucleotide (NAD)-dependent deacetylases, has recently been demonstrated to have neuroprotective effect in several models of neurodegenerative diseases. The present study attempts to determine whether SIRT1 has a neuroprotective effect in the model of TBI, and further to investigate the possible regulatory mechanism of neuron death. Thus, we employ transection model in vitro and weight-drop model in vivo to mimic the insults of TBI. The study shows that the expressions of SIRT1, phosphorylation extracellular signal-regulated kinase (p-ERK) and cleaved Caspase-3 are induced after trauma injury in vitro or in vivo. Furthermore, inhibiting SIRT1 by pharmacological inhibitor salermide or SIRT1 siRNA significantly promotes apoptotic neuron death and reduces ERK1/2 activation induced by mechanical injury in vitro and in vivo. Inhibition of ERK1/2 activation with PD98059 or U0126 (two mitogen activated protein kinase kinase inhibitors) in vitro and in vivo significantly attenuates the SIRT1 and cleaved Caspase-3 expression to protect neuron against TBI-induced apoptosis. These results reveal that SIRT1 plays a neuroprotective effect against neuronal apoptosis induced by TBI. The interactions between SIRT1 and MAPK/ERK pathway regulate neuronal apoptosis induced by mechanical trauma injury in vitro and in vivo. |
| Starting Page | 489 |
| Ending Page | 498 |
| Page Count | 10 |
| File Format | PDF HTM / HTML |
| DOI | 10.1016/j.expneurol.2012.07.004 |
| Alternate Webpage(s) | https://api.elsevier.com/content/article/pii/S0014488612002816 |
| Alternate Webpage(s) | https://www.sciencedirect.com/science/article/pii/S0014488612002816?dgcid=api_sd_search-api-endpoint |
| PubMed reference number | 22828134 |
| Alternate Webpage(s) | https://doi.org/10.1016/j.expneurol.2012.07.004 |
| Journal | Medline |
| Volume Number | 237 |
| Journal | Experimental Neurology |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
