Role of autophagy in human mesenchymal stem cells in response to irradiation

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Abstract

BACKGROUND:

Bone marrow mesenchymal stem cells can survive under the lethal dose of radiation in response to hematopoietic stem cells, and still maintain the typical characteristics of stem cells to promote hematopoietic recovery after radiation. However, autophagy is an important mechanism for cellular adaptation under stress, which may be involved in radiation tolerance of bone marrow mesenchymal stem cells.

OBJECTIVE:

To investigate the role of autophagy in human bone marrow mesenchymal stem cells in response to irradiation.

METHODS:

Passage 3 bone marrow mesenchymal stem cells cultured in vitro at logarithmic phase were collected and randomized into control, 3-mehyladenine, rapamycin, irradiation, irradiation+3-mehyladenine and irradiation+rapamycin groups. The autophagy reactions of bone marrow mesenchymal stem cells were regulated by 5 mmol/L 3-mehyladenine and 200 nmol/L rapamycin for 12 hours in the 3-mehyladenine and rapamycin groups, respectively. Two-hour 6 Gy X-ray irradiation was performed in the irradiation group and two complication groups undergoing 12-hour corresponding drug intervention.

RESULTS AND CONCLUSION:

The proportions of cells with autophagic vacuoles and apoptotic cells were higher in the irradiation group than the control group, moreover, autophagic+apoptotic cells were increased in the irradiation group. 3-mehyladenine intervention could decrease the proportion of cells with autophagic vacuoles, and increase the number of apoptotic cells. But there was no difference in the proportion of autophagic+apoptotic cells between the 3-mehyladenine and irradiation groups. After rapamycin intervention, the proportion of autophagic cells was higher than that in the irradiation group, but no difference in the proportion of apoptotic cells between the two grups, as well as there were no autophagic+apoptotic cells. The expression of microtubule-associated protein 1 light chain 3-II was ranked as follows: the control and 3-mehyladenine groups < irradiation+3-mehyladenine group < irradiation group < rapamycin group < irradiation+rapamycin group. These findings indicate that autophagy induced by irradiation could contribute to protecting bone marrow mesenchymal stem cells from irradiation injury.

Subject headings:

autophagy; radiation injuries; mesenchymal stem cells; radiotherapy; cytoskeleton

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