Iron overload adversely effects bone marrow haematogenesis via SIRT-SOD2-mROS in a process ameliorated by curcumin
| Autor: | Ruye Ma, Yuqing Dong, Kang Yu, Shenghui Zhang, Songfu Jiang, Shujuan Zhou, Siqian Wang, Yongyong Ma, Shanhu Qian, Haige Ye, Lan Sun, Zhijian Shen, Yifen Shi, Jianping Shen |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Mitochondrial ROS Programmed cell death Curcumin SIRT3 SOD2 Bone marrow damage Pharmacology Biochemistry Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Bone Marrow Sirtuin 3 medicine Autophagy Animals Humans Iron overload lcsh:QH573-671 Molecular Biology chemistry.chemical_classification Reactive oxygen species Superoxide Dismutase lcsh:Cytology Research Acetylation Cell Biology Hematopoiesis Mitochondria 030104 developmental biology medicine.anatomical_structure chemistry Cytoprotection 030220 oncology & carcinogenesis Bone marrow Reactive Oxygen Species |
| Zdroj: | Cellular & Molecular Biology Letters, Vol 26, Iss 1, Pp 1-15 (2021) Cellular & Molecular Biology Letters |
| ISSN: | 1689-1392 1425-8153 |
| Popis: | Background Iron overload, which is common in patients with haematological disorders, is known to have a suppressive effect on haematogenesis. However, the mechanism for this effect is still unclear. The antioxidant curcumin has been reported to protect against iron overload-induced bone marrow damage through an as-yet-unknown mechanism. Methods We established iron overload cell and mouse models. Mitochondrial reactive oxygen species (mROS) levels, autophagy levels and the SIRT3/SOD2 pathway were examined in the models and in the bone marrow of patients with iron overload. Results Iron overload was shown to depress haematogenesis and induce mitochondrion-derived superoxide anion-dependent autophagic cell death. Iron loading decreased SIRT3 protein expression, promoted an increase in SOD2, and led to the elevation of mROS. Overexpression of SIRT3 reversed these effects. Curcumin treatment ameliorated peripheral blood cells generation, enhanced SIRT3 activity, decreased SOD2 acetylation, inhibited mROS production, and suppressed iron loading-induced autophagy. Conclusions Our results suggest that curcumin exerts a protective effect on bone marrow by reducing mROS-stimulated autophagic cell death in a manner dependent on the SIRT3/SOD2 pathway. |
| Databáze: | OpenAIRE |
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