Goralska M, Harned J, Grimes A M, Fleisher L N, McGahan M C
Department of Anatomy, Physiology, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA.
Exp Eye Res. 1997 Mar;64(3):413-21. doi: 10.1006/exer.1996.0227.
A previous study demonstrated that ascorbic acid increased the concentration of the iron storage protein, ferritin. In cultured lens epithelial cells. The current study was designed to determine the mechanism by which ascorbic acid exerts this effect. Ascorbic acid increased both ferritin mRNA levels (by about 30%) and translation of ferritin (de novo synthesis was increased up to 15-fold) within 6 hr. Cycloheximide completely abolished the ability of ascorbic acid to increase ferritin levels, whereas actinomycin D only decreased it by about 30%. Therefore, the ascorbic-acid induced increase in ferritin concentration is due mainly to an increase in ferritin synthesis at the translational levels. This is a novel role for ascorbic acid. Addition of iron with ascorbic acid further increased de novo synthesis of ferritin, but this additive effect was only noted at a later time point (20 hr). Factors which decrease ferritin mRNA translation, such as the reducing agent dithiothreitol or the iron chelator desferrioxamine, reduced the ascorbic acid effect on de novo ferritin synthesis. The effects of ascorbic acid on ferritin mRNA levels may be mediated by its oxidation product, H2O2, since, like ascorbic acid, H2O2 increased ferritin mRNA levels by 30%. However, in contrast to the ascorbic acid-induced increase in translation of ferritin, H2O2 substantially decreased de novo ferritin synthesis. This effect of H2O2 could have physiological significance in eyes where concentrations of H2O2 in the aqueous humor are elevated. High levels of H2O2 could decrease the concentration of ferritin within the lens. Since ferritin sequesters iron and has been shown to decrease oxidative damage by limiting the availability of iron to catalyse free radical reactions, H2O2-induced reduction in ferritin concentration in the lens could have deleterious effects. The ability of ascorbic acid to increase ferritin concentration in lens epithelial cells could provide an additional protective mechanism for this antioxidant vitamin. The importance of ferritin to normal lens functioning is underscored by the recent finding that humans with a dominantly inherited abnormality in ferritin synthesis exhibit early bilateral cataracts.
先前的一项研究表明，在培养的晶状体上皮细胞中，抗坏血酸可提高铁储存蛋白铁蛋白的浓度。本研究旨在确定抗坏血酸发挥这种作用的机制。抗坏血酸在6小时内可使铁蛋白mRNA水平（约提高30%）和铁蛋白翻译（从头合成增加至15倍）均增加。放线菌酮完全消除了抗坏血酸提高铁蛋白水平的能力，而放线菌素D仅使其降低约30%。因此，抗坏血酸诱导的铁蛋白浓度增加主要是由于翻译水平上铁蛋白合成的增加。这是抗坏血酸的一个新作用。抗坏血酸与铁一起添加可进一步增加铁蛋白的从头合成，但这种相加作用仅在较晚的时间点（20小时）才被观察到。降低铁蛋白mRNA翻译的因素，如还原剂二硫苏糖醇或铁螯合剂去铁胺，可降低抗坏血酸对铁蛋白从头合成的作用。抗坏血酸对铁蛋白mRNA水平的影响可能由其氧化产物H2O2介导，因为与抗坏血酸一样，H2O2可使铁蛋白mRNA水平提高30%。然而，与抗坏血酸诱导的铁蛋白翻译增加相反，H2O2显著降低了铁蛋白的从头合成。H2O2的这种作用在房水中H2O2浓度升高的眼睛中可能具有生理意义。高水平的H2O2可降低晶状体中铁蛋白的浓度。由于铁蛋白螯合铁，并已被证明通过限制铁催化自由基反应的可用性来减少氧化损伤，H2O2诱导的晶状体中铁蛋白浓度降低可能具有有害影响。抗坏血酸增加晶状体上皮细胞中铁蛋白浓度的能力可为这种抗氧化维生素提供额外的保护机制。最近的一项发现强调了铁蛋白对晶状体正常功能的重要性，即铁蛋白合成存在显性遗传异常的人会出现早期双侧白内障。
