Iron Overload Adversely Effects Bone Marrow Haematogenesis via SIRT-SOD2-MROS in a Process Ameliorated by Curcumin
Background: Iron overload is common in patients with haematological disorders, and it is known to have a suppressive effect on haematogenesis. However, the mechanism by which iron overload affects haematogenesis is still unclear. The antioxidant curcumin has been reported to protect against iron overload-induced bone marrow damage, although the mechanism underlying this protective effect remains to be elucidated.
Methods: We established iron overload cell and mouse models. Mitochondrion-derived reactive oxygen species (mROS) levels, autophagy levels, and the SIRT3/SOD2 pathway were examined in these 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. These effects were reversed by the overexpression of SIRT3. Curcumin treatment ameliorated peripheral blood cells, enhanced SIRT3 activity, decreased SOD2 acetylation, inhibited mROS production, and suppressed iron loading-induced autophagy.
Conclusions: These 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.
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Posted 12 Jun, 2020
Iron Overload Adversely Effects Bone Marrow Haematogenesis via SIRT-SOD2-MROS in a Process Ameliorated by Curcumin
Posted 12 Jun, 2020
Background: Iron overload is common in patients with haematological disorders, and it is known to have a suppressive effect on haematogenesis. However, the mechanism by which iron overload affects haematogenesis is still unclear. The antioxidant curcumin has been reported to protect against iron overload-induced bone marrow damage, although the mechanism underlying this protective effect remains to be elucidated.
Methods: We established iron overload cell and mouse models. Mitochondrion-derived reactive oxygen species (mROS) levels, autophagy levels, and the SIRT3/SOD2 pathway were examined in these 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. These effects were reversed by the overexpression of SIRT3. Curcumin treatment ameliorated peripheral blood cells, enhanced SIRT3 activity, decreased SOD2 acetylation, inhibited mROS production, and suppressed iron loading-induced autophagy.
Conclusions: These 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.
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