Oligodendrocytes are the most iron-rich cells in the brain. Studies have shown that oligodendrocytes are very sensitive to oxidative stress, and iron overload is more likely to cause damage to oligodendrocytes. The purpose of this experiment was to investigate the damaging effect and mechanism of ferric ammonium citrate (FAC) on MO3.13 oligodendrocytes. In FAC treatment group, the intracellular iron concentration and intracellular reactive oxygen species were increased. There were no obvious changes in nucleus and chromatin, but increased mitochondrial membrane density, decreased mitochondrial cristae and mitochondrial length were observed. Glutathione peroxidase 4 (GPX4) expression was decreased, but the ratio of Bcl-2/Bax protein levels and cleaved caspase-3 expression did not change. Moreover, the iron chelator deferoxamine (DFO) and the ferroptosis inhibitor ferrostatin-1(Fer-1) could inhibit the upregulation of GPX4, which indicating that DFO and Fer-1 could inhibit ferroptosis in MO3.13 oligodendrocytes induced by iron overload. Furthermore, the phosphorylation level of p53 was not changed, while the ratio of protein expressions of p-Erk1/2/Erk1/2 were markedly increased. Taken together, our data suggest that iron overload induces ferroptosis but not apoptosis in oligodendrocytes. The mechanism may be related to mitogen-activated protein kinase pathway activation rather than p53 pathway activation.

少突胶质细胞是大脑中最富含铁的细胞。研究表明，少突胶质细胞对氧化应激非常敏感，铁过载更容易对少突胶质细胞造成损伤。本实验旨在探讨柠檬酸铁铵（FAC）对MO3.13少突胶质细胞的损伤作用及机制。在 FAC 治疗组中，细胞内铁浓度和细胞内活性氧增加。细胞核和染色质无明显变化，但线粒体膜密度增加，线粒体嵴减少，线粒体长度减少。谷胱甘肽过氧化物酶 4 (GPX4) 表达降低，但 Bcl-2/Bax 蛋白水平和裂解的 caspase-3 表达的比率没有改变。而且，铁螯合剂去铁胺(DFO)和铁死亡抑制剂ferrostatin-1(Fer-1)可以抑制GPX4的上调，说明DFO和Fer-1可以抑制铁过载诱导的MO3.13少突胶质细胞的铁死亡。此外，p53的磷酸化水平没有改变，而p-Erk1/2/Erk1/2的蛋白表达比例明显增加。综上所述，我们的数据表明，铁过载会诱导少突胶质细胞铁死亡，但不会诱导细胞凋亡。该机制可能与丝裂原活化蛋白激酶通路激活有关，而不是与 p53 通路激活有关。p53的磷酸化水平没有变化，而p-Erk1/2/Erk1/2的蛋白表达比值明显升高。综上所述，我们的数据表明，铁过载会诱导少突胶质细胞铁死亡，但不会诱导细胞凋亡。该机制可能与丝裂原活化蛋白激酶通路激活有关，而不是与 p53 通路激活有关。p53的磷酸化水平没有变化，而p-Erk1/2/Erk1/2的蛋白表达比值明显升高。综上所述，我们的数据表明，铁过载会诱导少突胶质细胞铁死亡，但不会诱导细胞凋亡。该机制可能与丝裂原活化蛋白激酶通路激活有关，而不是与 p53 通路激活有关。