Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8479199 | Neurochemistry International | 2014 | 10 Pages |
Abstract
Both oxidative stress and endoplasmic reticulum stress (ER stress) have been linked to pathogenesis of neurodegenerative diseases. Our previous study has shown that l-carnitine may function as an antioxidant to inhibit H2O2-induced oxidative stress in neuroblastoma SH-SY5Y cells. To further explore the neuroprotection of l-carnitine, here we study the effects of l-carnitine on the ER stress response in H2O2-induced SH-SY5Y cell injury. Our results showed that l-carnitine pretreatment could increase cell viability; inhibit apoptosis and ROS accumulation caused by H2O2 or tunicamycin (TM). l-carnitine suppress the endoplasmic reticulum dilation and activation of ER stress-associated proteins including glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein-homologous protein (CHOP), JNK, Bax and Bim induced by H2O2 or TM. In addition, H2O2-induced cell apoptosis and activation of ER stress can also be attenuated by antioxidant N-acetylcysteine (NAC), CHOP siRNA and the inhibitor of ER stress 4-phenylbutyric acid (4-PBA). Taken together, our results demonstrated that H2O2 could trigger both oxidative stress and ER stress in SH-SY5Y cells, and ER stress participated in SH-SY5Y apoptosis mediated by H2O2-induced oxidative stress. CHOP/Bim or JNK/Bim-dependent ER stress signaling pathways maybe related to the neuroprotective effects of l-carnitine against H2O2-induced apoptosis and oxidative injury.
Keywords
DCFDAJnkCCAAT/enhancer-binding protein-homologous proteinESRtunicamycinNACERK2′,7′-dichlorodihydrofluorescein diacetatec-Jun N-terminal protein kinaseGRP78/BiPMAPKN-acetylcysteineROSHydrogen peroxideER stressEndoplasmic reticulum stressl-CarnitineOxidative stressCHOPApoptosisSH-SY5Y cellsextracellular-signal regulated kinaseH2O2glucose-regulated protein 78mitogen-activated protein kinaseReactive oxygen species
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Authors
Junli Ye, Yantao Han, Xuehong Chen, Jing Xie, Xiaojin Liu, Shunhong Qiao, Chunbo Wang,