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甲基汞靶向光感受器外段。

Methylmercury targets photoreceptor outer segments.

机构信息

Canadian Light Source Inc. , 44 Innovation Boulevard, Saskatoon, SK S7N 2V3, Canada.

出版信息

ACS Chem Biol. 2013 Oct 18;8(10):2256-63. doi: 10.1021/cb4004805. Epub 2013 Aug 19.

Abstract

Human populations experience widespread low level exposure to organometallic methylmercury compounds through consumption of fish and other seafood. At higher levels, methylmercury compounds specifically target nervous systems, and among the many effects of their exposure are visual disturbances, including blindness, which previously were thought to be due to methylmercury-induced damage to the visual cortex. Here, we employ high-resolution X-ray fluorescence imaging using beam sizes of 500 × 500 and 250 × 250 nm(2) to investigate the localization of mercury at unprecedented resolution in sections of zebrafish larvae ( Danio rerio ), a model developing vertebrate. We demonstrate that methylmercury specifically targets the outer segments of photoreceptor cells in both the retina and pineal gland. Methylmercury distribution in both tissues was correlated with that of sulfur, which, together with methylmercury's affinity for thiolate donors, suggests involvement of protein cysteine residues in methylmercury binding. In contrast, in the lens, the mercury distribution was different from that of sulfur, with methylmercury specifically accumulating in the secondary fiber cells immediately underlying the lens epithelial cells rather than in the lens epithelial cells themselves. Since methylmercury targets two main eye tissues (lens and photoreceptors) that are directly involved in visual perception, it now seems likely that the visual disruption associated with methylmercury exposure in higher animals including humans may arise from direct damage to photoreceptors, in addition to injury of the visual cortex.

摘要

人类通过食用鱼类和其他海鲜,广泛地接触到低水平的有机金属甲基汞化合物。在较高水平下,甲基汞化合物特别针对神经系统,其暴露的许多影响之一是视觉障碍,包括失明,以前认为这是由于甲基汞对视觉皮层的损伤所致。在这里,我们使用束斑尺寸为 500×500 和 250×250nm2 的高分辨率 X 射线荧光成像,以在斑马鱼幼虫(Danio rerio)切片中以前所未有的分辨率研究汞的定位,斑马鱼幼虫是一种正在发育的脊椎动物模型。我们证明甲基汞特别针对视网膜和松果体中光感受器细胞的外节。两种组织中的甲基汞分布与硫的分布相关,硫与甲基汞对硫醇供体的亲和力一起,表明在甲基汞结合中涉及蛋白质半胱氨酸残基。相比之下,在晶状体中,汞的分布与硫不同,甲基汞特异性地积聚在直接位于晶状体上皮细胞下方的次级纤维细胞中,而不是在晶状体上皮细胞本身中。由于甲基汞针对两种主要的眼部组织(晶状体和光感受器),这些组织直接参与视觉感知,因此现在看来,包括人类在内的高等动物接触甲基汞后出现的视觉障碍可能不仅源于视觉皮层损伤,还可能源于光感受器的直接损伤。

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