Decreased cell survival and DNA repair capacity after UVC irradiation in association with down-regulation of GRP78/BiP in human RSa cells.
In contrast to extensive studies on the roles of molecular chaperones, such as heat shock proteins, there are only a few reports about the roles of GRP78/BiP, an endoplasmic reticulum (ER) stress-induced molecular chaperone, in mammalian cell responses to DNA-damaging stresses. To investigate whether GRP78/BiP is involved in resistance to a DNA-damaging agent, UVC (principally 254 nm in wavelength), we established human cells with down-regulation of GRP78/BiP by transfection of human RSa cells with antisense cDNA for GRP78/BiP. We found that the transfected cells showed higher sensitivity to UVC-induced cell death than control cells transfected with the vector alone. In the antisense-cDNA transfected cells, the removal capacities of the two major types of UVC-damaged DNA (thymine dimers and (6-4) photoproducts) in vivo and DNA synthesis activity of whole cell extracts to repair UVC-irradiated plasmids in vitro were remarkably decreased compared with those in the control cells. Furthermore, the antisense-cDNA transfected cells also showed slightly higher sensitivity to cisplatin-induced cell death than the control cells. Cisplatin-induced DNA damage is primarily repaired by nucleotide excision repair, like UVC-induced DNA damage. The present results suggest that GRP78/BiP plays a protective role against UVC-induced cell death possibly via nucleotide excision repair, at least in the human RSa cells tested.
Zhai
Ling
L
Department of Environmental Biochemistry, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chiba 260-8670, Japan.
Kita
Kazuko
K
Wano
Chieko
C
Wu
Yuping
Y
Sugaya
Shigeru
S
Suzuki
Nobuo
N
D016923:Cell Death / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects*; D016373:DNA, Antisense / Q000235:genetics; D015536:Down-Regulation; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011740:Pyrimidine Dimers / Q000378:metabolism; D014466:Ultraviolet Rays
D016373:DNA, Antisense; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D011740:Pyrimidine Dimers; D004247:DNA; D002945:Cisplatin