l-Carnitine attenuates H2O2-induced neuron apoptosis via inhibition of endoplasmic reticulum stress

Publication date: December 2014 Source:Neurochemistry International, Volume 78 Author(s): Junli Ye , Yantao Han , Xuehong Chen , Jing Xie , Xiaojin Liu , Shunhong Qiao , Chunbo Wang 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...
Source: Neurochemistry International - Category: Neuroscience Source Type: research