Pyruvate metabolism: A therapeutic opportunity in radiation-induced skin injury

Hyun Yoo, Jeong Wook Kang, Dong Won Lee, Sang Ho Oh, Yun Sil Lee, Eun Jung Lee, Jaeho Cho

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)504-510
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume460
Issue number3
DOIs
Publication statusPublished - 2015 May 2

Bibliographical note

Funding Information:
This work was supported by the Nuclear Research and Development Program ( NRF-2011-0031695 ) and by the Radiation Technology Research and Development Program ( NRF-2013M2A2A7042978 ) through the National Research Foundation of Korea, funded by the Ministry of Science, ICT & Future Planning as well as by a faculty research grant from Yonsei University College of Medicine for 2014 ( 6-2014-0031 ).

Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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