title: Pyruvate metabolism: A therapeutic opportunity in radiation-induced skin injury.
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.
authors: Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, South Korea.
authors: Hyun
authors: H
authors: Yoo
authors: Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, South Korea.
authors: Jeong Wook
authors: JW
authors: Kang
authors: Department of Plastic Surgery, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, South Korea.
authors: Dong Won
authors: DW
authors: Lee
authors: Department of Dermatology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, South Korea.
authors: Sang Ho
authors: SH
authors: Oh
authors: College of Pharmacy & Division of Life and Pharmaceutical Sciences, Ewah Womans University, Seoul 120-750, South Korea.
authors: Yun-Sil
authors: YS
authors: Lee
authors: Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, South Korea.
authors: Eun-Jung
authors: EJ
authors: Lee
authors: Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, South Korea. Electronic address: jjhmd@yuhs.ac.
authors: Jaeho
authors: J
authors: Cho
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D051379:Mice; D041681:NIH 3T3 Cells; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011773:Pyruvates / Q000378:metabolism*; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000628:therapy*; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000293:injuries / Q000528:radiation effects*
chemical_list: D016207:Cytokines; C000631435:Pdk2 protein, mouse; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011773:Pyruvates; D017346:Protein Serine-Threonine Kinases
keywords: Pyruvate dehydrogenase kinase; Radiation; Skin injury