Arsenic induces sustained impairment of skeletal muscle and muscle progenitor cell ultrastructure and bioenergetics.
Arsenic induces sustained impairment of skeletal muscle and muscle progenitor cell ultrastructure and bioenergetics.
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DOI：
10.1016/j.freeradbiomed.2014.06.012
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发表时间：
2014-09
影响因子：
7.4
通讯作者：
Barchowsky, Aaron
中科院分区：
文献类型：
--
作者：
Ambrosio, Fabrisia;Brown, Elke;Stolz, Donna;Ferrari, Ricardo;Goodpaster, Bret;Deasy, Bridget;Distefano, Giovanna;Roperti, Alexandra;Cheikhi, Amin;Garciafigueroa, Yesica;Barchowsky, Aaron
美国有超过 400 万人，全球有超过 1.4 亿人每天接触受砷污染的饮用水。人类接触的浓度范围从低于当前限值 10 µg/L 到超过 1 mg/L，其中 100 µg/L 会促进大部分接触者患病。尽管最近人们越来越关注砷暴露后的肌病，但临床症状的致病机制仍然知之甚少。这项研究检验了砷会导致持久的肌肉线粒体功能障碍并损害新陈代谢的假设。与未暴露的对照组相比，暴露于含有 100μg/L 亚砷酸盐的饮用水 5 周的小鼠表现出肌肉功能受损、线粒体肌病和耗氧量改变，这些都伴随着线粒体融合基因转录的增加。对照组和暴露肌肉之间的无机砷或其单甲基和二甲基代谢物的水平没有差异，证实砷不会在肌肉中积累。然而，与从未暴露的小鼠中分离的细胞相比，从暴露的小鼠中分离的肌肉祖细胞再现了异常的肌纤维表型，并且对氧化应激具有更强的抵抗力，产生更多的活性氧，并表现出自噬性线粒体形态。这些可能的适应不良氧化应激反应引起的病理变化让我们深入了解由于暴露于这种常见的环境污染物而导致的肌肉功能下降。
Over 4 million individuals in the US, and over 140 million individuals worldwide, are exposed daily to arsenic-contaminated drinking water. Human exposures can range from below the current limit of 10 µg/L to over 1 mg/L, with 100 µg/L promoting disease in a large portion of those exposed. Although increased attention has recently been paid to myopathy following arsenic exposure, the pathogenic mechanisms underlying clinical symptoms remain poorly understood. This study tested the hypothesis that arsenic induces lasting muscle mitochondrial dysfunction and impairs metabolism. When compared to non-exposed controls, mice exposed to drinking water containing 100µg/L arsenite for 5 weeks demonstrated impaired muscle function, mitochondrial myopathy, and altered oxygen consumption that were concomitant with increased mitochondrial fusion gene transcription. There was no difference in levels of inorganic arsenic or its mononomethyl- and dimethyl- metabolites between controls and exposed muscles, confirming that arsenic does not accumulate in muscle. Nevertheless, muscle progenitor cells isolated from exposed mice recapitulated the aberrant myofiber phenotype and were more resistant to oxidative stress, generated more reactive oxygen species, and displayed autophagic mitochondrial morphology, as compared to cells isolated from non-exposed mice. These pathological changes from a possible maladaptive oxidative stress response provide insight into declines in muscle functioning caused by exposure to this common environmental contaminant.
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影响因子：
3.8
作者：
Lantz RC;Chau B;Sarihan P;Witten ML;Pivniouk VI;Chen GJ
通讯作者：
Chen GJ
DOI：
10.1083/jcb.200108150
发表时间：
2002-05-27
期刊：
The Journal of cell biology
影响因子：
--
作者：
Qu-Petersen Z;Deasy B;Jankowski R;Ikezawa M;Cummins J;Pruchnic R;Mytinger J;Cao B;Gates C;Wernig A;Huard J
通讯作者：
Huard J
影响因子：
3.2
作者：
Li, Yan;Sun, Xiuhua;Kang, Y James
通讯作者：
Kang, Y James
DOI：
10.1081/ese-120016887
发表时间：
2003-01-01
影响因子：
2.1
作者：
Mukherjee, SC;Rahman, MM;Chakraborti, D
通讯作者：
Chakraborti, D
影响因子：
4.1
作者：
Ambrosio, Fabrisia;Ferrari, Ricardo J.;Huard, Johnny
通讯作者：
Huard, Johnny