Enhanced expression of transferrin receptor confers UV-resistance in human and monkey cells.
One of the most intriguing biological subjects is cell-surface molecules that regulate the susceptibility of human cells to cell-killing effects after irradiation with far-ultraviolet light (UV, principally 254 nm wavelength). Human RSa cells have unusual sensitivity to UV-induced cell-killing. We searched for molecules on the cell-surface of RSa cells that were present in different amounts as compared to a variant of these cells, UV(r)-1 cells, which have increased resistance to UV cell-killing. Among the 21 molecules examined, the amount of transferrin receptor (TfR) protein was found to be 2-fold higher in UV(r)-1 cells compared with in RSa cells. The amounts of this protein were also higher in the UV-resistant hematopoietic cell lines, CEM6 and Daudi, as compared to the UV-sensitive cell lines, Molt4 and 697. Culturing of UV(r)-1 cells in a medium containing anti-transferrin antibodies resulted in sensitization of the cells to UV cell-killing as demonstrated by colony formation assay. Similar results were observed by treatment of the cells with TfR siRNA. In contrast, overexpression of TfR protein led to a resistance to UV cell-killing in RSa cells and monkey COS7 cells as demonstrated by both colony formation and apoptosis assay. In TfR-overexpressing cells, reduction of p53 and Bax protein was observed after UV-irradiation. Thus, TfR expression appears to be involved in the regulation of UV-resistance, possibly via modulation of the amount of p53 and Bax protein.
Chen
Zheng
Z
Department of Environmental Biochemistry, Graduate School of Medicine, Chiba University, Japan.
Nomura
Jun
J
Suzuki
Toshikazu
T
Suzuki
Nobuo
N
D000818:Animals; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects*; D019556:COS Cells; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology* / Q000528:radiation effects*; D002522:Chlorocebus aethiops; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000502:physiology*; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
D011990:Receptors, Transferrin