Oxidation of low density lipoprotein (LDL) has been proposed to be involved in the pathogenesis of atherosclerosis. We have previously shown that LDL can be oxidised by iron in lysosomes. As the iron-storage protein ferritin might enter lysosomes by autophagy, we have investigated the ability of ferritin to catalyse LDL oxidation at lysosomal pH. LDL was incubated with ferritin at 37 °C and pH 4.5 and its oxidation monitored spectrophotometrically at 234 nm by the formation of conjugated dienes and by measuring oxidised lipids by HPLC or a tri-iodide assay. Iron released from ferritin was measured using the ferrous iron chelator bathophenanthroline and by ultrafiltration followed by atomic absorption spectroscopy. LDL was oxidised effectively by ferritin (0.05–0.2 μM). The oxidation at lysosomal pH (pH 4.5) was much faster than at pH 7.4. Ferritin increased cholesteryl linoleate hydroperoxide, total lipid hydroperoxides and 7-ketocholesterol. Iron was released from ferritin at acidic pH. The iron chelators, diethylenetriaminepentaacetate and EDTA, and antioxidant N,N׳-diphenyl-p-phenylenediamine inhibited the oxidation considerably, but not entirely. The antioxidant tempol did not inhibit the initial oxidation of LDL, but inhibited its later oxidation. Cysteamine, a lysosomotropic antioxidant, inhibited the initial oxidation of LDL in a concentration-dependent manner, however, the lower concentrations exhibited a pro-oxidant effect at later times, which was diminished and then abolished as the concentration increased. These results suggest that ferritin might play a role in lysosomal LDL oxidation and that antioxidants that accumulate in lysosomes might be a novel therapy for atherosclerosis.

低密度脂蛋白（LDL）的氧化已被认为与动脉粥样硬化的发病机制有关。先前我们已经表明，LDL可以被溶酶体中的铁氧化。由于铁存储蛋白铁蛋白可能通过自噬进入溶酶体，因此我们研究了铁蛋白在溶酶体pH值下催化LDL氧化的能力。将LDL与铁蛋白在37°C和pH 4.5下孵育，并通过形成共轭二烯并通过HPLC或三碘化物测定法测量氧化脂质，在234 nm处分光光度法监测其氧化。使用亚铁螯合剂邻菲咯啉和超滤，然后进行原子吸收光谱法测定从铁蛋白中释放的铁。LDL被铁蛋白（0.05–0.2μM）有效氧化。在溶酶体pH（pH 4.5）下的氧化比在pH 7.4下的氧化快得多。铁蛋白增加了胆固醇亚油酸氢过氧化物，总脂质氢过氧化物和7-酮胆固醇。在酸性pH下铁从铁蛋白中释放出来。铁螯合剂，二乙撑三胺五乙酸盐和EDTA以及抗氧化剂N，N ׳-二苯基-对苯二胺极大地抑制了氧化，但没有完全抑制。抗氧化剂tempol不会抑制LDL的初始氧化，但会抑制其后来的氧化。半胱氨酸，溶血同质性抗氧化剂，以浓度依赖的方式抑制LDL的初始氧化，但是，较低的浓度在以后的时间表现出促氧化作用，随着浓度的增加，其逐渐减弱，然后消失。这些结果表明，铁蛋白可能在溶酶体的LDL氧化中起作用，并且溶酶体中积累的抗氧化剂可能是动脉粥样硬化的新疗法。