title: Caspase-4 directly activates caspase-9 in endoplasmic reticulum stress-induced apoptosis in SH-SY5Y cells.
abstract: The present study investigated the function of caspase-4 in endoplasmic reticulum (ER) stress-induced apoptosis in human neuronal cell line SH-SY5Y. Tunicamycin, which is known to induce ER stress, activated both caspase-9 and caspase-4, and the activation of caspase-4 preceded that of caspase-9. The caspase-4 inhibitor LEVD-CHO suppressed both the apoptosis and caspase-9 activation. In addition, human recombinant active caspase-4 cleaved wild type and D330A mutant substituted Asp-330 for alanine of human recombinant procaspase-9, but did not cleave D315A mutant substituted Asp-315 for alanine. These results suggest that caspase-4 directly activates caspase-9 by the processing of procaspase-9 at Asp-315 in ER stress-induced neuronal apoptosis.
authors.affiliation: Department of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka 573-0101, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Yamamuro
authors.forename: Takashi
authors.initials: T
authors.lastname: Kishino
authors.forename: Yu
authors.initials: Y
authors.lastname: Ohshima
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshioka
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kimura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kasai
authors.forename: Sadaaki
authors.initials: S
authors.lastname: Maeda
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053453:Caspase 9 / Q000378:metabolism*; D061945:Caspase Inhibitors; D053471:Caspases, Initiator / Q000378:metabolism*; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D013312:Stress, Physiological; D014415:Tunicamycin / Q000494:pharmacology*
chemical_list: D061945:Caspase Inhibitors; D011994:Recombinant Proteins; D014415:Tunicamycin; C093516:CASP4 protein, human; D053453:Caspase 9; D053471:Caspases, Initiator