Dataset Information

Human AHH1 cells heavy ion irradiation LC-MSMS

ABSTRACT: Heavy ion radiotherapy has unfolded a great promise for cancer therapy. Understanding the cellular response mechanism to heavy ion radiation is required for exploring the measures of overcoming the devastating side effects. Here, we performed a quantitative proteomics to investigate the mechanism of carbon heavy ion irradiation on human AHH-1 lymphoblastoid cells. Totally we identified 4602 proteins and quantified 4569 proteins among which with high coverage on mitochondria. After stringent filtering, we found 290 proteins were significantly up-regulated and 16 proteins were down-regulated. Functional analysis revealed that these up-regulated proteins specifically enriched in the process of DNA damage repair, mitochondrial ribosome and especially mitochondrial respiratory chain, which occupied approximately fifty percent of the accumulated proteins. Bioinformatics analysis and functional study demonstrated that these up- regulated mitochondrial respiratory chain proteins enhanced ATP production and simultaneously ROS releasing. More importantly, the increased ROS led to organelle secondary injury and the lagged DNA double strand breaks. Consistently, the expression of antioxidant enzymes was up-regulated for free radical scavenging. The mechanism of lagged secondary injury originated from disturbing of mitochondrial respiratory chain, the “target” outside nuclear, explored here may provide a novel target for cell self-repairing against heavy ion radiation induced cellular damage.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Suspension Culture, Leukocyte

SUBMITTER: Peng-Cheng Fan

LAB HEAD: Ping Xu

PROVIDER: PXD008351 | Pride | 2018-11-07

REPOSITORIES: Pride

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Quantitative proteomics reveals mitochondrial respiratory chain as a dominant target for carbon ion radiation: Delayed reactive oxygen species generation caused DNA damage.

Fan Peng-Cheng PC Zhang Yao Y Wang Yu Y Wei Wei W Zhou Yan-Xia YX Xie Yi Y Wang Xin X Qi Ying-Zi YZ Chang Lei L Jia Zheng-Ping ZP Zhou Zhe Z Guan Hua H Zhang Hong H Xu Ping P Zhou Ping-Kun PK

Free radical biology & medicine 20181103

Heavy ion radiotherapy has shown great promise for cancer therapy. Understanding the cellular response mechanism to heavy ion radiation is required to explore measures of overcoming devastating side effects. Here, we performed a quantitative proteomic analysis to investigate the mechanism of carbon ion irradiation on human AHH-1 lymphoblastoid cells. We identified 4602 proteins and quantified 4569 proteins showing high coverage in the mitochondria. Data are available via ProteomeXchange with ide ...[more]

PMID: 30395972

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Project description:The growing number of particle treatment facilities worldwide and patients treated with particles instead of X-rays marks the upcoming rearrangement of modern radiotherapy. Especially for tumors being difficult to access and for tumors that are resistant to conventional X-ray treatment particle radiotherapy is a beneficial technology. At the Heidelberg Ion Beam Therapy Center (HIT) patients are treated with this technology since 2009 as it offers clear benefits. Contrary to X-rays, which show an exponential dose decrease (after reaching electron equilibrium) with increasing tissue depth, charged particles deposit most of their energy to a small region within the tissue with a sharp dose fall-off after the so-called Bragg peak. This precise dose localization enables further dose escalation within the tumor while sparing healthy tissue. Besides physical advantages, particle radiotherapy offers additional biological advantages. In radiobiology, the term relative-biological effectiveness (RBE) is defined as the ratio of X-rays dose to an alternative irradiation modality dose which produce the same biological effect (e.g. survival or number of DSBs). While protons have a relative biological effectiveness (RBE) comparable to X-rays, carbon ions are more effective in inducing DNA damage(1, 2) and are therefore especially useful for radioresistant tumors. This is due to the fact, that carbon ions induce clustered and direct DNA damage, which is considered to be less dependent on cell cycle stage, oxygen level, genetic background and hinders DNA repair mechanisms(3–6). Nevertheless, their exact mode of action and cellular mechanisms are largely unknown. We show the first comprehensive proteomic and phosphoproteomic study elucidating the cellular response to treatment with protons, carbon ions and X-rays. We found that 2h after treatment with these radiations negligible regulation occurred at protein expression level. But 181 phosphorylation sites were deregulated by ionizing radiation contributing mainly to DNA damage response functionalities. Interestingly we found 55 phosphorylation sites being differentially regulated between the radiations. Here, we observed protons and carbon ions producing equal cellular response whereas X-rays show altered regulation for certain phosphorylation sites. A subset of 28 phosphorylation sites being involved in the DNA damage response or differentially regulated between the ionizing radiations was selected for result confirmation.

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