title: L-carnitine attenuates H2O2-induced neuron apoptosis via inhibition of endoplasmic reticulum stress.
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.
authors.affiliation: Department of Pathophysiology, Medical College, Qingdao University, Qingdao, Shandong 266071, China. Electronic address: yejunli126@126.com.
authors.forename: Junli
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Pharmacology, Medical College, Qingdao University, Qingdao 266071, China.
authors.forename: Yantao
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Pharmacology, Medical College, Qingdao University, Qingdao 266071, China.
authors.forename: Xuehong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Medical College, Qingdao University, Qingdao 266071, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Pharmacy, Dezhou People's Hospital, Dezhou, China.
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Biological Sciences, University of Memphis, TN 38111, USA.
authors.forename: Shunhong
authors.initials: S
authors.lastname: Qiao
authors.affiliation: Department of Pharmacology, Medical College, Qingdao University, Qingdao 266071, China.
authors.forename: Chunbo
authors.initials: C
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002331:Carnitine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002331:Carnitine
keywords: Apoptosis; Endoplasmic reticulum stress; Oxidative stress; SH-SY5Y cells; l-Carnitine