Effects of carbon ion irradiation and X-ray irradiation on the ubiquitylated protein accumulation

C-ion radiotherapy is associated with improved local control and survival in several types of tumors. Although C-ion irradiation is widely reported to effectively induce DNA damage in tumor cells, the effects of irradiation on proteins, such as protein stability or degradation in response to radiati...

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Main Authors: ISOZAKI, TETSURO, FUJITA, MAYUMI, YAMADA, SHIGERU, IMADOME, KAORI, SHOJI, YOSHIMI, YASUDA, TAKESHI, NAKAYAMA, FUMIAKI, IMAI, TAKASHI, MATSUBARA, HISAHIRO
Format: Online
Language:English
Published: D.A. Spandidos 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902063/
id pubmed-4902063
recordtype oai_dc
spelling pubmed-49020632016-06-24 Effects of carbon ion irradiation and X-ray irradiation on the ubiquitylated protein accumulation ISOZAKI, TETSURO FUJITA, MAYUMI YAMADA, SHIGERU IMADOME, KAORI SHOJI, YOSHIMI YASUDA, TAKESHI NAKAYAMA, FUMIAKI IMAI, TAKASHI MATSUBARA, HISAHIRO Articles C-ion radiotherapy is associated with improved local control and survival in several types of tumors. Although C-ion irradiation is widely reported to effectively induce DNA damage in tumor cells, the effects of irradiation on proteins, such as protein stability or degradation in response to radiation stress, remain unknown. We aimed to compare the effects of C-ion and X-ray irradiation focusing on the cellular accumulation of ubiquitylated proteins. Cells from two human colorectal cancer cell lines, SW620 and SW480, were subjected to C-ion or X-ray irradiation and determination of ubiquitylated protein levels. High levels of ubiquitylated protein accumulation were observed in the C-ion-irradiated SW620 with a peak at 3 Gy; the accumulation was significantly lower in the X-ray-irradiated SW620 at all doses. Enhanced levels of ubiquitylated proteins were also detected in C-ion or X-ray-irradiated SW480, however, those levels were significantly lower than the peak detected in the C-ion-irradiated SW620. The levels of irradiation-induced ubiquitylated proteins decreased in a time-dependent manner, suggesting that the proteins were eliminated after irradiation. The treatment of C-ion-irradiated SW620 with a proteasome inhibitor (epoxomicin) enhanced the cell killing activity. The accumulated ubiquitylated proteins were co-localized with γ-H2AX, and with TP53BP1, in C-ion-irradiated SW620, indicating C-ion-induced ubiquitylated proteins may have some functions in the DNA repair system. Overall, we showed C-ion irradiation strongly induces the accumulation of ubiquitylated proteins in SW620. These characteristics may play a role in improving the therapeutic ratio of C-ion beams; blocking the clearance of ubiquitylated proteins may enhance sensitivity to C-ion radiation. D.A. Spandidos 2016-05-05 /pmc/articles/PMC4902063/ /pubmed/27175736 http://dx.doi.org/10.3892/ijo.2016.3504 Text en Copyright: © Isozaki et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author ISOZAKI, TETSURO
FUJITA, MAYUMI
YAMADA, SHIGERU
IMADOME, KAORI
SHOJI, YOSHIMI
YASUDA, TAKESHI
NAKAYAMA, FUMIAKI
IMAI, TAKASHI
MATSUBARA, HISAHIRO
spellingShingle ISOZAKI, TETSURO
FUJITA, MAYUMI
YAMADA, SHIGERU
IMADOME, KAORI
SHOJI, YOSHIMI
YASUDA, TAKESHI
NAKAYAMA, FUMIAKI
IMAI, TAKASHI
MATSUBARA, HISAHIRO
Effects of carbon ion irradiation and X-ray irradiation on the ubiquitylated protein accumulation
author_facet ISOZAKI, TETSURO
FUJITA, MAYUMI
YAMADA, SHIGERU
IMADOME, KAORI
SHOJI, YOSHIMI
YASUDA, TAKESHI
NAKAYAMA, FUMIAKI
IMAI, TAKASHI
MATSUBARA, HISAHIRO
author_sort ISOZAKI, TETSURO
title Effects of carbon ion irradiation and X-ray irradiation on the ubiquitylated protein accumulation
title_short Effects of carbon ion irradiation and X-ray irradiation on the ubiquitylated protein accumulation
title_full Effects of carbon ion irradiation and X-ray irradiation on the ubiquitylated protein accumulation
title_fullStr Effects of carbon ion irradiation and X-ray irradiation on the ubiquitylated protein accumulation
title_full_unstemmed Effects of carbon ion irradiation and X-ray irradiation on the ubiquitylated protein accumulation
title_sort effects of carbon ion irradiation and x-ray irradiation on the ubiquitylated protein accumulation
description C-ion radiotherapy is associated with improved local control and survival in several types of tumors. Although C-ion irradiation is widely reported to effectively induce DNA damage in tumor cells, the effects of irradiation on proteins, such as protein stability or degradation in response to radiation stress, remain unknown. We aimed to compare the effects of C-ion and X-ray irradiation focusing on the cellular accumulation of ubiquitylated proteins. Cells from two human colorectal cancer cell lines, SW620 and SW480, were subjected to C-ion or X-ray irradiation and determination of ubiquitylated protein levels. High levels of ubiquitylated protein accumulation were observed in the C-ion-irradiated SW620 with a peak at 3 Gy; the accumulation was significantly lower in the X-ray-irradiated SW620 at all doses. Enhanced levels of ubiquitylated proteins were also detected in C-ion or X-ray-irradiated SW480, however, those levels were significantly lower than the peak detected in the C-ion-irradiated SW620. The levels of irradiation-induced ubiquitylated proteins decreased in a time-dependent manner, suggesting that the proteins were eliminated after irradiation. The treatment of C-ion-irradiated SW620 with a proteasome inhibitor (epoxomicin) enhanced the cell killing activity. The accumulated ubiquitylated proteins were co-localized with γ-H2AX, and with TP53BP1, in C-ion-irradiated SW620, indicating C-ion-induced ubiquitylated proteins may have some functions in the DNA repair system. Overall, we showed C-ion irradiation strongly induces the accumulation of ubiquitylated proteins in SW620. These characteristics may play a role in improving the therapeutic ratio of C-ion beams; blocking the clearance of ubiquitylated proteins may enhance sensitivity to C-ion radiation.
publisher D.A. Spandidos
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902063/
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