title: Inhibition of sphingomyelin synthase 1 affects ceramide accumulation and hydrogen peroxide-induced apoptosis in Neuro-2a cells.
abstract: Oxidative stress plays a key role in brain injury after cerebral ischemia-reperfusion, which contributes toward excessive apoptosis of nerve cells. Therefore, it would be beneficial to identify a therapy that could interfere with the progression of apoptosis and protect the brain from ischemia-reperfusion injury. As ceramide, a well-known second messenger of apoptosis, can be metabolized by sphingomyelin synthase 1 (SMS1), recent research has focused on the link between SMS1 and apoptosis in different cells. To investigate whether SMS1 is involved in the process of oxidative stress-induced apoptosis in neurons and to explore the possible underlying mechanism, we treated mouse neuroblastoma Neuro-2A (N2a) cells with hydrogen peroxide (H2O2). Incubation with H2O2 significantly upregulated the expression of SMS1, increased the intracellular levels of ceramide and sphingomyelin synthase activity, and induced apoptosis. Moreover, pretreatment of N2a cells with D609, an sphingomyelin synthase inhibitor, or SMS1-silencing RNA (siRNA) further increased ceramide and potentiated H2O2-induced apoptosis which could be reversed by SB203580 (a p38 inhibitor). Thus, our study has shown that SMS1 regulates ceramide levels in N2a cells and plays a potent protective role in this oxidative stress-induced apoptosis partly through the p38 pathway.
authors.affiliation: aDepartment of Neurology, Second Xiangya Hospital, Central South University bDepartment of Pulmonary, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Ranran
authors.initials: R
authors.lastname: Tu
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D045744:Cell Line, Tumor; D002518:Ceramides / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000008:administration & dosage; D051379:Mice; D009636:Norbornanes; D018384:Oxidative Stress; D013859:Thiocarbamates; D013871:Thiones / Q000008:administration & dosage; D017855:Transferases (Other Substituted Phosphate Groups) / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D001952:Bridged-Ring Compounds; D002518:Ceramides; D009636:Norbornanes; D013859:Thiocarbamates; D013871:Thiones; C046498:tricyclodecane-9-yl-xanthogenate; D006861:Hydrogen Peroxide; C556686:Sgms1 protein, mouse; D017855:Transferases (Other Substituted Phosphate Groups)