Quantitative proteomic analysis of the effects of melatonin treatment for mice suffered from small intestinal damage induced by γ-ray radiation

Abstract

Purpose

Intestinal damage induced by radiation exposure is a major clinic concern of radiotherapy for patients with abdominal or pelvic tumor. Melatonin (N-acetyl-5-methoxytryptamine) is likely be an ideal radioprotector to protect individuals from radiation exposure. The study aimed to define the role of melatonin in small intestinal damage caused by abdominal irradiation (ABI).

Materials and methods

30-day survival rate and pathological histology of the intestines from melatonin-treated mice after 13 Gy ABI exposure was first detected. Next, quantitative proteomics analysis of the small intestines tissue was examined and GO term and KEGG pathways analysis were performed.

Results

Melatonin treatment before ABI exposure significantly increased 30-day survival rate to 83% and ameliorated damage to the intestinal epithelial cells. Melatonin significantly altered the proteins profile of the small intestines following irradiation. For the irradiated mice treated with melatonin in comparison with the irradiated mice, the enriched GO terms were mainly involved in defense response to other organism (BP, GO: 0098542), response to other organism (BP, GO: 0051707), anion transmembrane transporter activity (MF, GO: 0008509), and secondary active transmembrane transporter activity (MF, GO: 0015291). In the process of antioxidant activity (MF, GO: 0016209), melatonin treatment prior to radiation exhibited high protein levels of Sod3 and Gpx3. The markedly KEGG pathways for melatonin treatment prior to radiation mainly included protein digestion and absorption (ko 04974) and mineral absorption (ko 04978). p53 signaling pathway and DNA repair pathways were enriched in melatonin treated mice. The amount of radiation-induced DNA damage and the cell apoptosis of the small intestines was decreased in the melatonin-treated mice.

Conclusions

Melatonin may protect small intestines from radiation damage through increasing DNA repair and decreasing cell apoptosis of the small intestines. Our data provided perspective for the study of melatonin in mitigating ABI-caused intestinal damage.

Keywords:

• Melatonin
• intestinal damage
• abdominal irradiation
• radioprotection

Disclosure statement

The authors declare that they have no competing interests.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China [31971168, 31670859, 81772243, 81803172, 81803167, and 31800703], CAMS Innovation Fund for Medical Science [2019-T2M-2-006, 2017-I2M-1-016], China Postdoctoral Science Foundation [2018M630106], Natural Science Foundation of Tianjin [18JCYBJC26800, 18JCQNJC12300, and 17JCYBJC42700], the Fundamental Research Funds for the Central Universities (10023201601602), the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences [2017-1001-08 and 2018RC310020] and the Youth Teachers Fund of Peking Union Medical College [2014zlgc0755].

Notes on contributors

Qin Wang

Qin Wang, PhD, is a Research Fellow of Department of Radiation Biology, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.

Yan Wang

Yan Wang, PhD, is an Associate Research Fellow of Department of Radiation Biology, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.

Liqing Du

Liqing Du, PhD, is a Research Fellow of Department of Radiation Biology, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.

Chang Xu

Chang Xu, PhD, is an Associate Research Fellow of Department of Radiation Biology, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.

Yang Liu

Yang Liu, PhD, is an Associate Research Fellow of Department of Radiation Biology, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.

Qiang Liu

Qiang Liu, PhD, is a Principal Investigator at Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.

Saijun Fan

Saijun Fan, PhD, is a Principal Investigator at Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.