title: Space radiation exposure persistently increased leptin and IGF1 in serum and activated leptin-IGF1 signaling axis in mouse intestine.
abstract: Travel into outer space is fraught with risk of exposure to energetic heavy ion radiation such as (56)Fe ions, which due to its high linear energy transfer (high-LET) characteristics deposits higher energy per unit volume of tissue traversed and thus more damaging to cells relative to low-LET radiation such as γ rays. However, estimates of human health risk from energetic heavy ion exposure are hampered due to lack of tissue specific in vivo molecular data. We investigated long-term effects of (56)Fe radiation on adipokines and insulin-like growth factor 1 (IGF1) signaling axis in mouse intestine and colon. Six- to eight-week-old C57BL/6J mice were exposed to 1.6 Gy of (56)Fe ions. Serum and tissues were collected up to twelve months post-irradiation. Serum was analyzed for leptin, adiponectin, IGF1, and IGF binding protein 3. Receptor expressions and downstream signaling pathway alterations were studied in tissues. Irradiation increased leptin and IGF1 levels in serum, and IGF1R and leptin receptor expression in tissues. When considered along with upregulated Jak2/Stat3 pathways and cell proliferation, our data supports the notion that space radiation exposure is a risk to endocrine alterations with implications for chronic pathophysiologic changes in gastrointestinal tract.
authors: Department of Biochemistry and Molecular &Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
authors: Shubhankar
authors: S
authors: Suman
authors: Department of Biochemistry and Molecular &Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
authors: Santosh
authors: S
authors: Kumar
authors: Department of Biochemistry and Molecular &Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.|Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Albert J
authors: AJ
authors: Fornace
authors: Department of Biochemistry and Molecular &Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
authors: Kamal
authors: K
authors: Datta
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D049109:Cell Proliferation / Q000528:radiation effects; D003106:Colon / Q000378:metabolism / Q000528:radiation effects; D004195:Disease Models, Animal; D020450:Heavy Ions / Q000009:adverse effects; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000528:radiation effects*; D007503:Iron Isotopes / Q000009:adverse effects*; D020738:Leptin / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D000069079:Radiation Exposure / Q000009:adverse effects; D017526:Receptor, IGF Type 1; D054411:Receptors, Leptin / Q000378:metabolism; D017451:Receptors, Somatomedin / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects
chemical_list: D052242:Adiponectin; C000597236:IGF1R protein, human; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D007503:Iron Isotopes; C515448:LEPR protein, human; D020738:Leptin; D054411:Receptors, Leptin; D017451:Receptors, Somatomedin; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1