title: Reactive oxygen species and p38 MAPK regulate Bax translocation and calcium redistribution in salubrinal-induced apoptosis of EBV-transformed B cells.
abstract: Salubrinal is a specific eIF2α phosphatase inhibitor that inhibits ER stress-mediated apoptosis. However, maintaining hyper-phosphorylated eIF2α state with high doses of salubrinal treatment promotes apoptosis in some cancer cells. In this report, we found that salubrinal induced apoptosis of EBV-transformed B cells. Notably, salubrinal induced ROS generation and p38 MPAK activation, which then induced expression of FasL. Moreover, salubrinal subsequently led to activation of caspases, calcium redistribution, Bax translocation, cytochrome c release, and apoptosis. These findings suggest that salubrinal may be a novel therapeutic approach for EBV-associated malignant diseases.
authors: Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan 614-735, Republic of Korea.
authors: Ga Bin
authors: GB
authors: Park
authors: Yeong Seok
authors: YS
authors: Kim
authors: Hyun-Kyung
authors: HK
authors: Lee
authors: Hyunkeun
authors: H
authors: Song
authors: Seonghan
authors: S
authors: Kim
authors: Dae-Ho
authors: DH
authors: Cho
authors: Dae Young
authors: DY
authors: Hur
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002461:Cell Line, Transformed; D002934:Cinnamates / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D020717:Eukaryotic Initiation Factor-2B / Q000037:antagonists & inhibitors / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000378:metabolism*; D051025:bcl-Associated Death Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D002934:Cinnamates; D020717:Eukaryotic Initiation Factor-2B; D053222:Fas Ligand Protein; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; C496827:salubrinal; D045304:Cytochromes c; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases; D013890:Thiourea; D002118:Calcium