title: Possible involvement of both endoplasmic reticulum-and mitochondria-dependent pathways in thapsigargin-induced apoptosis in human neuroblastoma SH-SY5Y cells.
abstract: Recently, it has been shown that endoplasmic reticulum (ER) stress causes apoptosis. However, the mechanism of the ER stress-dependent pathway is not fully understood. In human neuroblastoma SH-SY5Y cells, we detected a caspase-12-like protein that has a molecular mass (approximately 60 kDa) similar to that of mouse caspase-12. Thapsigargin, an inhibitor of ER-associated Ca(2+)-ATPase, induced the degradation of caspase-12-like protein. In addition, the degradation of caspases-9 and -3, cleavage of poly(ADP-ribose) polymerase, DNA fragmentation, and cell death were also observed. Pretreatment with phorbol-12-myristate-13-acetate, which induces the expression of antiapoptotic Bcl-2, inhibited thapsigargin-induced degradation of caspases-9 and -3, but not caspase-12-like protein degradation. A caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp(OCH(3))-CH(2)F, inhibited the degradation of caspase-12-like protein, but not that of caspases-9 and -3. These results suggest that thapsigargin may induce the activation of both ER- and mitochondria-dependent pathways in human SH-SY5Y cells.
authors.affiliation: Department of Neurobiology, Kyoto Pharmaceutical University, Kyoto, Japan. yo.kita@mb.kyoto-phu.ac.jp
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyamura
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Takata
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Inden
authors.forename: Daiju
authors.initials: D
authors.lastname: Tsuchiya
authors.forename: Kumi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Taniguchi
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009447:Neuroblastoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D019284:Thapsigargin / Q000494:pharmacology*
chemical_list: D019284:Thapsigargin; D020169:Caspases