title: Suppression of okadaic acid-induced apoptosis by overexpression of calpastatin in human UV(r)-1 cells.
abstract: Proteolytic systems have various involvements in apoptotic pathways. To understand the role of calpain in apoptosis, calpastatin, a specific inhibitor of calpain, was overexpressed in human UV(r)-1 fibroblasts by transfection of its cDNA. The elevated expression of calpastatin resulted in decreased survival in the presence of okadaic acid (OA) but in no apparent alteration in the sensitivity toward other drugs such as 5-fluorouracil, mitomycin C and methotrexate. After treatment with OA, a typical apoptotic DNA ladder was observed in control vector-transfected cells but not in calpastatin-transfected cells. This indicates that OA-induced apoptosis was suppressed by overexpression of calpastatin. Further immunoblot analysis showed that the OA-induced hyperphosphorylation of c-Jun was inhibited in calpastatin-transfected cells. This might be involved in the resistance to OA-induced cell death in calpastatin-overproducing cells.
authors.affiliation: Department of Biochemistry, School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, Japan.
authors.forename: X J
authors.initials: XJ
authors.lastname: Chi
authors.forename: T
authors.initials: T
authors.lastname: Hiwasa
authors.forename: M
authors.initials: M
authors.lastname: Maki
authors.forename: S
authors.initials: S
authors.lastname: Sugaya
authors.forename: J
authors.initials: J
authors.lastname: Nomura
authors.forename: K
authors.initials: K
authors.lastname: Kita
authors.forename: N
authors.initials: N
authors.lastname: Suzuki
mesh_terms: D017209:Apoptosis; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology*; D014162:Transfection; D014466:Ultraviolet Rays; D051025:bcl-Associated Death Protein
chemical_list: C494819:BAD protein, human; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D051025:bcl-Associated Death Protein; D019319:Okadaic Acid; C033668:calpastatin; D020928:Mitogen-Activated Protein Kinases