Novel therapeutic approach targeting TrkB receptor aganist radiation injure

2015 Fiscal Year Final Research Report

• Project/Area Number: 26861032
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: National Institute of Radiological Sciences
• Principal Investigator: Tomiyama Ken-ichi 国立研究開発法人放射線医学総合研究所, 緊急被ばく医療研究センター, 博士研究員 (20584064)
• Co-Investigator(Renkei-kenkyūsha): Obara Chizuka 国立研究開発法人放射線医学総合研究所, 緊急被ばく医療研究センター, 研究員 (90415977)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: radiation injure / BDNF / IEC-6 / MSC

Outline of Final Research Achievements

Here, we demonstrate that brain-derived neurotrophic factor (BDNF), an endogenous ligand for tyrosine kinase B (TrkB) receptor, protect IEC-6 cells against gamma (γ)-irradiation damage. IEC-6 was exposed with 4Gy of γ-irradiation and then challenged BDNF treatment. After 24 hours, γ-irradiation-induced cell death of IEC-6 and expression of cleaved caspase-3 were decreased. Further examination shows that BDNF suppresses apoptosis of IEC-6 induced by irradiation damage through an increase of Bcl-2/Bax ratio. BDNF significantly enhanced the phosphorylation of Akt and ERK1/2 proteins by subsequent to irradiation and ameliorated the expression of Bcl-2 protein. These data also indicates that PI3K/AKT and/or ERK1/2 pathway activated by BDNF plays important role for IEC-6 survival after γ-irradiation. Therefore, BDNF may be therapeutically useful to attenuate the intestinal injury caused by radiation.

Free Research Field

放射線生物学