PURPOSE: Radiation-induced bystander effects (RIBE) imply the involvement of complex signaling mechanisms, which can be mediated by extracellular vesicles (EVs). Using an in vivo model, we investigated EV-transmitted RIBE in blood plasma and radiation effects on plasma EV miRNA profiles. MATERIALS AND METHODS: C57Bl/6 mice were total-body irradiated with 0.1 and 2 Gy, bone marrow-derived EVs were isolated, and injected systemically into naive, 'bystander' animals. Proteome profiler antibody array membranes were used to detect alterations in plasma, both in directly irradiated and bystander mice. MiRNA profile of plasma EVs was determined by PCR array. RESULTS: M-CSF and pentraxin-3 levels were increased in the blood of directly irradiated and bystander mice both after low and high dose irradiations, CXCL16 and lipocalin-2 increased after 2 Gy in directly irradiated and bystander mice, CCL5 and CCL11 changed in bystander mice only. Substantial overlap was found in the cellular pathways regulated by those miRNAs whose level were altered in EVs isolated from the plasma of mice irradiated with 0.1 and 2 Gy. Several of these pathways have already been associated with bystander responses. CONCLUSION: Low and high dose effects overlapped both in EV-mediated alterations in signaling pathways leading to RIBE and in their systemic manifestations.
PURPOSE: Radiation-induced bystander effects (RIBE) imply the involvement of complex signaling mechanisms, which can be mediated by extracellular vesicles (EVs). Using an in vivo model, we investigated EV-transmitted RIBE in blood plasma and radiation effects on plasma EV miRNA profiles. MATERIALS AND METHODS: C57Bl/6 mice were total-body irradiated with 0.1 and 2 Gy, bone marrow-derived EVs were isolated, and injected systemically into naive, 'bystander' animals. Proteome profiler antibody array membranes were used to detect alterations in plasma, both in directly irradiated and bystander mice. MiRNA profile of plasma EVs was determined by PCR array. RESULTS:M-CSF and pentraxin-3 levels were increased in the blood of directly irradiated and bystander mice both after low and high dose irradiations, CXCL16 and lipocalin-2 increased after 2 Gy in directly irradiated and bystander mice, CCL5 and CCL11 changed in bystander mice only. Substantial overlap was found in the cellular pathways regulated by those miRNAs whose level were altered in EVs isolated from the plasma of mice irradiated with 0.1 and 2 Gy. Several of these pathways have already been associated with bystander responses. CONCLUSION: Low and high dose effects overlapped both in EV-mediated alterations in signaling pathways leading to RIBE and in their systemic manifestations.
Authors: Brian S Canter; Calvin N Leung; J Christopher Fritton; Tom Bäck; Didier Rajon; Edouard I Azzam; Roger W Howell Journal: Mol Cancer Res Date: 2021-05-26 Impact factor: 5.852
Authors: Ebrahim Afshinnekoo; Ryan T Scott; Matthew J MacKay; Eloise Pariset; Egle Cekanaviciute; Richard Barker; Simon Gilroy; Duane Hassane; Scott M Smith; Sara R Zwart; Mayra Nelman-Gonzalez; Brian E Crucian; Sergey A Ponomarev; Oleg I Orlov; Dai Shiba; Masafumi Muratani; Masayuki Yamamoto; Stephanie E Richards; Parag A Vaishampayan; Cem Meydan; Jonathan Foox; Jacqueline Myrrhe; Eric Istasse; Nitin Singh; Kasthuri Venkateswaran; Jessica A Keune; Hami E Ray; Mathias Basner; Jack Miller; Martha Hotz Vitaterna; Deanne M Taylor; Douglas Wallace; Kathleen Rubins; Susan M Bailey; Peter Grabham; Sylvain V Costes; Christopher E Mason; Afshin Beheshti Journal: Cell Date: 2020-11-25 Impact factor: 66.850
Authors: Mona G Alharbi; Seok Hee Lee; Aaser M Abdelazim; Islam M Saadeldin; Mosleh M Abomughaid Journal: Biomed Res Int Date: 2021-07-20 Impact factor: 3.411