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. 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. 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. 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.

中文翻译：

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在姜黄素改善的过程中，铁过载通过 SIRT-SOD2-mROS 对骨髓造血产生不利影响

众所周知，铁过载在血液系统疾病患者中很常见，它对造血有抑制作用。然而，这种作用的机制仍不清楚。据报道，抗氧化剂姜黄素可以通过一种未知的机制防止铁过载引起的骨髓损伤。我们建立了铁过载细胞和小鼠模型。在模型和铁过载患者的骨髓中检查了线粒体活性氧 (mROS) 水平、自噬水平和 SIRT3/SOD2 途径。铁过载显示抑制造血并诱导线粒体衍生的超氧阴离子依赖性自噬细胞死亡。铁负荷降低了 SIRT3 蛋白的表达，促进了 SOD2 的增加，并导致了 mROS 的升高。SIRT3 的过度表达逆转了这些影响。姜黄素治疗改善了外周血细胞的生成，增强了 SIRT3 活性，降低了 SOD2 乙酰化，抑制了 mROS 的产生，并抑制了铁负荷诱导的自噬。我们的结果表明，姜黄素通过以依赖于 SIRT3/SOD2 通路的方式减少 mROS 刺激的自噬细胞死亡，从而对骨髓发挥保护作用。