title: Autophagy correlates with maintenance of salivary gland function following radiation.
abstract: The current standard of care for head and neck cancer includes surgical resection of the tumor followed by targeted head and neck radiation. This radiotherapy results in a multitude of negative side effects in adjacent normal tissues. Autophagy is a cellular mechanism that could be targeted to ameliorate these side effects based on its role in cellular homeostasis. In this study, we utilized Atg5(f/f);Aqp5-Cre mice which harbor a conditional knockout of Atg5, in salivary acinar cells. These autophagy-deficient mice display increased radiosensitivity. Treatment of wild-type mice with radiation did not robustly induce autophagy following radiotherapy, however, using a model of preserved salivary gland function by IGF-1-treatment prior to irradiation, we demonstrate increased autophagosome formation 6-8 hours following radiation. Additionally, administration of IGF-1 to Atg5(f/f);Aqp5-Cre mice did not preserve physiological function. Thus, autophagy appears to play a beneficial role in salivary glands following radiation and pharmacological induction of autophagy could alleviate the negative side effects associated with therapy for head and neck cancer.
authors.affiliation: Department of Nutritional Sciences, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Morgan-Bathke
authors.affiliation: Department of Nutritional Sciences, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Grace A
authors.initials: GA
authors.lastname: Hill
authors.affiliation: Department of Nutritional Sciences, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Zoey I
authors.initials: ZI
authors.lastname: Harris
authors.affiliation: Department of Molecular Pharmacology, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
authors.forename: Her H
authors.initials: HH
authors.lastname: Lin
authors.affiliation: Cancer Biology Graduate Interdisciplinary Program, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Alex M
authors.initials: AM
authors.lastname: Chibly
authors.affiliation: Department of Pathology, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Rob R
authors.initials: RR
authors.lastname: Klein
authors.affiliation: Department of Nutritional Sciences, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Randy
authors.initials: R
authors.lastname: Burd
authors.affiliation: Department of Molecular Pharmacology, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
authors.forename: David K
authors.initials: DK
authors.lastname: Ann
authors.affiliation: Department of Nutritional Sciences, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Kirsten H
authors.initials: KH
authors.lastname: Limesand
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001343:Autophagy; D000071187:Autophagy-Related Protein 5; D015153:Blotting, Western; D049109:Cell Proliferation / Q000528:radiation effects; D002478:Cells, Cultured; D005260:Female; D005720:Gamma Rays; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D019426:Integrases / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D011836:Radiation Tolerance; D012469:Salivary Glands / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects
chemical_list: C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; C045073:Cre recombinase; D019426:Integrases