title: Extracellular recombinant annexin II confers UVC-radiation resistance and increases the Bcl-xL to Bax protein ratios in human UVC-radiation-sensitive cells.
abstract: In this study, we found that refractoriness to ultraviolet (UVC) light-induced cell death was increased in UVC-radiation-sensitive cells derived from Cockayne syndrome patients when the cells were precultured in medium supplemented with recombinant annexin II (rANX II). In CS3BES cells, an immortal cell line derived from Cockayne syndrome patients, the rANX II supplementation-induced UVC-radiation resistance was suppressed by treatment with an anti-annexin II antibody and EGTA. The amount of biotinylated annexin II on the cell surface increased in the rANX II-supplemented cells but did not increase in the cells that were cotreated with rANX II and EGTA. The capacity to remove UVC-radiation-damaged DNA, (6-4) photoproducts and cyclobutane pyrimidine dimers, was the same in cells that were precultured with rANX II and in control cells that did not receive rANX II supplementation. The rANX II supplementation-induced UVC-radiation resistance was also observed in nucleotide excision repair-deficient cells and xeroderma pigmentosum group A-downregulated cells. The Bcl-xL to Bax protein ratios, an index of survival activity in cells exposed to lethal stresses, were increased in the cells that had been precultured in rANX II for 24 h prior to UVC irradiation. Treatment with a phosphatidylinositol 3-kinase inhibitor suppressed the increased UVC-radiation resistance and Bcl-xL to Bax ratios in the cells with rANX II supplementation. Furthermore, downregulation of Bcl-xL by siRNA transfection also suppressed the UVC-radiation resistance that was induced by rANX II supplementation. These results suggest that the increase in the Bcl-xL to Bax ratios may be associated with enhanced resistance to UVC-radiation-induced cell death.
authors.affiliation: a Department of Environmental Biochemistry, Graduate School of Medicine, Chiba University, Inohana, Chuou-ku, Chiba 260-8670, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kita
authors.forename: Katsuo
authors.initials: K
authors.lastname: Sugita
authors.forename: Shi-Ping
authors.initials: SP
authors.lastname: Chen
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Suzuki
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sugaya
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Yuan-Hu
authors.initials: YH
authors.lastname: Jin
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Satoh
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Tong
authors.forename: Nobuo
authors.initials: N
authors.lastname: Suzuki
mesh_terms: D017306:Annexin A2 / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003057:Cockayne Syndrome / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects / Q000528:radiation effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011836:Radiation Tolerance / Q000187:drug effects* / Q000528:radiation effects; D011994:Recombinant Proteins / Q000494:pharmacology*; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism*
chemical_list: D017306:Annexin A2; D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein