Pyruvate metabolism: A therapeutic opportunity in radiation-induced skin injury
- 주제(키워드) Pyruvate dehydrogenase kinase , Radiation , Skin injury
- 등재 SCIE, SCOPUS
- 발행기관 Academic Press Inc.
- 발행년도 2015
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000118648
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.bbrc.2015.03.060
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Ionizing radiation is used to treat a range of cancers. Despite recent technological progress, radiation therapy can damage the skin at the administration site. The specific molecular mechanisms involved in this effect have not been fully characterized. In this study, the effects of pyruvate, on radiation-induced skin injury were investigated, including the role of the pyruvate dehydrogenase kinase 2 (PDK2) signaling pathway. Next generation sequencing (NGS) identified a wide range of gene expression differences between the control and irradiated mice, including reduced expression of PDK2. This was confirmed using Q-PCR. Cell culture studies demonstrated that PDK2 overexpression and a high cellular pyruvate concentration inhibited radiation-induced cytokine expression. Immunohistochemical studies demonstrated radiation-induced skin thickening and gene expression changes. Oral pyruvate treatment markedly downregulated radiation-induced changes in skin thickness and inflammatory cytokine expression. These findings indicated that regulation of the pyruvate metabolic pathway could provide an effective approach to the control of radiation-induced skin damage. © 2015 Elsevier Inc. All rights reserved.
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