Acute Proteomic Changes in the Lung after WTLI in a Mouse Model: Identification of Potential Initiating Events for Delayed Effects of Acute Radiation Exposure

TY - JOUR

T1 - Acute Proteomic Changes in the Lung after WTLI in a Mouse Model

T2 - Identification of Potential Initiating Events for Delayed Effects of Acute Radiation Exposure

AU - Huang, Weiliang

AU - Yu, Jianshi

AU - Jones, Jace W.

AU - Carter, Claire L.

AU - Jackson, I. Lauren

AU - Vujaskovic, Zeljko

AU - Macvittie, Thomas J.

AU - Kane, Maureen A.

N1 - Publisher Copyright: © Lippincott Williams & Wilkins.

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Radiation-induced lung injury is a delayed effect of acute radiation exposure resulting in pulmonary pneumonitis and fibrosis. Molecular mechanisms that lead to radiation-induced lung injury remain incompletely understood. Using a murine model of whole-thorax lung irradiation, C57BL/6J mice were irradiated at 8, 10, 12, and 14 Gy and assayed at day 1, 3, and 6 postexposure and compared to nonirradiated (sham) controls. Tryptic digests of lung tissues were analyzed by liquid chromatography-tandem mass spectrometry on a Waters nanoLC instrument coupled to a Thermo Scientific Q Exactive hybrid quadrupole-orbitrap mass spectrometer. Pathway and gene ontology analysis were performed with Qiagen Ingenuity, Panther GO, and DAVID databases. A number of trends were identified in the proteomic data, including protein changes greater than 10 fold, protein changes that were consistently up regulated or down regulated at all time points and dose levels interrogated, time and dose dependency of protein changes, canonical pathways affected by irradiation, changes in proteins that serve as upstream regulators, and proteins involved in key processes including inflammation, radiation, and retinoic acid signaling. The proteomic profiling conducted here represents an untargeted systems biology approach to identify acute molecular events that could potentially be initiating events for radiation-induced lung injury.

AB - Radiation-induced lung injury is a delayed effect of acute radiation exposure resulting in pulmonary pneumonitis and fibrosis. Molecular mechanisms that lead to radiation-induced lung injury remain incompletely understood. Using a murine model of whole-thorax lung irradiation, C57BL/6J mice were irradiated at 8, 10, 12, and 14 Gy and assayed at day 1, 3, and 6 postexposure and compared to nonirradiated (sham) controls. Tryptic digests of lung tissues were analyzed by liquid chromatography-tandem mass spectrometry on a Waters nanoLC instrument coupled to a Thermo Scientific Q Exactive hybrid quadrupole-orbitrap mass spectrometer. Pathway and gene ontology analysis were performed with Qiagen Ingenuity, Panther GO, and DAVID databases. A number of trends were identified in the proteomic data, including protein changes greater than 10 fold, protein changes that were consistently up regulated or down regulated at all time points and dose levels interrogated, time and dose dependency of protein changes, canonical pathways affected by irradiation, changes in proteins that serve as upstream regulators, and proteins involved in key processes including inflammation, radiation, and retinoic acid signaling. The proteomic profiling conducted here represents an untargeted systems biology approach to identify acute molecular events that could potentially be initiating events for radiation-induced lung injury.

KW - biological indicators

KW - ionizing

KW - lungs

KW - radiation

KW - radiation damage

KW - rodent

UR - https://www.scopus.com/pages/publications/85061206548

U2 - 10.1097/HP.0000000000000956

DO - 10.1097/HP.0000000000000956

M3 - Article

C2 - 30652977

SN - 0017-9078

VL - 116

SP - 503

EP - 515

JO - Health physics

JF - Health physics

IS - 4

ER -