title: High and low doses of ionizing radiation induce different secretome profiles in a human skin model.
abstract: It is postulated that secreted soluble factors are important contributors of bystander effect and adaptive responses observed in low dose ionizing radiation. Using multidimensional liquid chromatography-mass spectrometry based proteomics, we quantified the changes of skin tissue secretome--the proteins secreted from a full thickness, reconstituted 3-dimensional skin tissue model 48 hr after exposure to 3, 10 and 200 cGy of X-rays. Overall, 135 proteins showed statistical significant difference between the sham (0 cGy) and any of the irradiated groups (3, 10 or 200 cGy) on the basis of Dunnett adjusted t-test; among these, 97 proteins showed a trend of downregulation and 9 proteins showed a trend of upregulation with increasing radiation dose. In addition, there were 21 and 8 proteins observed to have irregular trends with the 10 cGy irradiated group either having the highest or the lowest level among all three radiated doses. Moreover, two proteins, carboxypeptidase E and ubiquitin carboxyl-terminal hydrolase isozyme L1 were sensitive to ionizing radiation, but relatively independent of radiation dose. Conversely, proteasome activator complex subunit 2 protein appeared to be sensitive to the dose of radiation, as rapid upregulation of this protein was observed when radiation doses were increased from 3, to 10 or 200 cGy. These results suggest that different mechanisms of action exist at the secretome level for low and high doses of ionizing radiation.
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, United States of America.
authors.forename: Qibin
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Computational Biology and Bioinformatics, Pacific Northwest National Laboratory, Richland, Washington, United States of America.
authors.forename: Melissa
authors.initials: M
authors.lastname: Matzke
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, United States of America.
authors.forename: Athena A
authors.initials: AA
authors.lastname: Schepmoes
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, United States of America.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Moore
authors.affiliation: Computational Biology and Bioinformatics, Pacific Northwest National Laboratory, Richland, Washington, United States of America.
authors.forename: Bobbie-Jo
authors.initials: BJ
authors.lastname: Webb-Robertson
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, United States of America.
authors.forename: Zeping
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, United States of America.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Monroe
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, United States of America.
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Qian
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, United States of America.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Smith
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, United States of America.
authors.forename: William F
authors.initials: WF
authors.lastname: Morgan
mesh_terms: D006801:Humans; D008954:Models, Biological; D020543:Proteome / Q000378:metabolism*; D012867:Skin / Q000378:metabolism* / Q000528:radiation effects; D046509:Tissue Culture Techniques; D014965:X-Rays
chemical_list: D020543:Proteome