Helmcke Kirsten J, Syversen Tore, Miller David M, Aschner Michael
Pharmacology Department, Vanderbilt University Medical Center, Nashville, TN 37232-0414, USA.
Toxicol Appl Pharmacol. 2009 Oct 15;240(2):265-72. doi: 10.1016/j.taap.2009.03.013. Epub 2009 Mar 31.
The rising prevalence of methylmercury (MeHg) in seafood and in the global environment provides an impetus for delineating the mechanism of the toxicity of MeHg. Deleterious effects of MeHg have been widely observed in humans and in other mammals, the most striking of which occur in the nervous system. Here we test the model organism, Caenorhabditis elegans (C. elegans), for MeHg toxicity. The simple, well-defined anatomy of the C. elegans nervous system and its ready visualization with green fluorescent protein (GFP) markers facilitated our study of the effects of methylmercuric chloride (MeHgCl) on neural development. Although MeHgCl was lethal to C. elegans, induced a developmental delay, and decreased pharyngeal pumping, other traits including lifespan, brood size, swimming rate, and nervous system morphology were not obviously perturbed in animals that survived MeHgCl exposure. Despite the limited effects of MeHgCl on C. elegans development and behavior, intracellular mercury (Hg) concentrations (<or=3 ng Hg/mg protein) in MeHgCl-treated nematodes approached levels that are highly toxic to mammals. If MeHgCl reaches these concentrations throughout the animal, this finding indicates that C. elegans cells, particularly neurons, may be less sensitive to MeHgCl toxicity than mammalian cells. We propose, therefore, that C. elegans should be a useful model for discovering intrinsic mechanisms that confer resistance to MeHgCl exposure.
海鲜及全球环境中甲基汞(MeHg)的普遍程度不断上升,这为阐明甲基汞毒性机制提供了动力。甲基汞的有害影响在人类和其他哺乳动物中已被广泛观察到,其中最显著的影响发生在神经系统。在此,我们以模式生物秀丽隐杆线虫(C. elegans)来测试甲基汞的毒性。秀丽隐杆线虫神经系统简单且结构明确,并且可以通过绿色荧光蛋白(GFP)标记轻松实现可视化,这便于我们研究氯化甲基汞(MeHgCl)对神经发育的影响。尽管MeHgCl对秀丽隐杆线虫具有致死性,会导致发育延迟并降低咽部抽吸功能,但在经受MeHgCl暴露后存活下来的动物中,包括寿命、产卵量、游泳速度和神经系统形态等其他特征并未受到明显干扰。尽管MeHgCl对秀丽隐杆线虫的发育和行为影响有限,但经MeHgCl处理的线虫细胞内汞(Hg)浓度(≤3 ng Hg/mg蛋白质)接近对哺乳动物具有高毒性的水平。如果MeHgCl在整个动物体内都达到这些浓度,这一发现表明秀丽隐杆线虫细胞,尤其是神经元,可能比哺乳动物细胞对MeHgCl毒性的敏感性更低。因此,我们认为秀丽隐杆线虫应该是发现赋予对MeHgCl暴露抗性的内在机制的有用模型。