Shujuan Zhou1, Lan Sun1, Shanhu Qian1, Yongyong Ma1, Ruye Ma1, Yuqing Dong1, Yifen Shi1, Songfu Jiang1, Haige Ye1, Zhijian Shen1, Shenghui Zhang1, Jianping Shen2, Kang Yu3, Siqian Wang4. 1. Department of Haematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China. 2. Department of Haematology, The First Affiliated Hospital of Zhejiang Chinese Medical University; The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, 310006, Zhejiang, People's Republic of China. shengjianping@163.com. 3. Department of Haematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China. 20442947@qq.com. 4. Department of Prosthodontics, School & Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China. wsq982004@163.com.
Abstract
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.
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.
Entities:
Keywords:
Autophagy; Bone marrow damage; Curcumin; Iron overload; Mitochondrial ROS
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