Uncontrolled oxidative stress production, especially in the outer retina is one of the causes of retinal degenerations. Mitochondria are considered the principal source of oxidative stress. However, a Reactive Oxygen Intermediates (ROI) production in the retinal photoreceptor layer seems to depend also on the expression of an extramitochondrial oxidative phosphorylation (OxPhos) machinery in the rod outer segments (OS). In fact, OS conduct aerobic metabolism, producing ATP through oxygen consumption, although it is devoid of mitochondria. As diterpenes display an antioxidant effect, we have evaluated the effect Manool, extracted from Salvia tingitana, on the extramitochondrial OxPhos and the ROI production in the retinal rod OS. Results confirm that the OxPhos machinery is ectopically expressed in the OS and that F₁F_o-ATP synthase is a target of Manool, which inhibited the OS ATP synthesis, binding the F₁ moiety with high affinity, as analysed by molecular docking. Moreover, the overall slowdown of OxPhos metabolism reduced the ROI production elicited in the OS by light exposure, in vitro. In conclusion, data are consistent with the antioxidant properties of Salvia spp., suggesting its ability to lower oxidative stress production, a primary risk factor for degenerative retinal diseases.

中文翻译：

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从丹参提取的二萜甘露醇通过抑制线粒体外 F1Fo ATP 合酶降低视网膜杆外段自由基的产生

不受控制的氧化应激产生，尤其是在外层视网膜是视网膜变性的原因之一。线粒体被认为是氧化应激的主要来源。然而，视网膜光感受器层中反应性氧中间体 (ROI) 的产生似乎也取决于杆状外段 (OS) 中线粒体外氧化磷酸化 (OxPhos) 机制的表达。事实上，OS 进行有氧代谢，通过耗氧量产生 ATP，尽管它没有线粒体。由于二萜表现出抗氧化作用，我们评估了从丹参提取的Manool 的作用，关于线粒体外 OxPhos 和视网膜杆 OS 中的 ROI 产生。结果证实，OxPhos 机制在 OS 中异位表达，并且 F ₁ F _o -ATP 合酶是 Manool 的靶标，Manool 抑制 OS ATP 合成，以高亲和力结合 F ₁部分，如通过分子对接分析。此外，OxPhos 代谢的整体放缓降低了体外曝光在 OS 中引起的 ROI 产生。总之，数据与鼠尾草的抗氧化特性一致，表明其能够降低氧化应激的产生，这是退行性视网膜疾病的主要危险因素。