The putative multidrug resistance protein MRP-7 inhibits methylmercury-associated animal toxicity and dopaminergic neurodegeneration in Caenorhabditis elegans.
The putative multidrug resistance protein MRP-7 inhibits methylmercury-associated animal toxicity and dopaminergic neurodegeneration in Caenorhabditis elegans.
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DOI：
10.1111/jnc.12515
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发表时间：
2014-03
影响因子：
4.7
通讯作者：
Nass R
中科院分区：
文献类型：
--
作者：
VanDuyn N;Nass R
Parkinson’s disease (PD) is the most prevalent neurodegenerative motor disorder worldwide, and results in the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta. Gene-environment interactions are believed to play a significant role in the vast majority of PD cases, yet the toxicants and the associated genes involved in the neuropathology are largely ill-defined. Recent epidemiological and biochemical evidence suggests that methylmercury (MeHg) may be an environmental toxicant that contributes to the development of PD. Here we report that a gene coding for the putative multidrug resistance protein MRP-7 in Caenorhabditis elegans (C. elegans) modulates whole animal and DA neuron sensitivity to MeHg. In this study we demonstrate that genetic knockdown of MRP-7 results in a 2-fold increase in Hg levels and a dramatic increase in stress response proteins associated with the endoplasmic reticulum, golgi apparatus, and mitochondria, as well as an increase in MeHg-associated animal death. Chronic exposure to low concentrations of MeHg induces MRP-7 gene expression, while exposures in MRP-7 genetic knockdown animals results in a loss of DA neuron integrity without affecting whole animal viability. Furthermore, transgenic animals expressing a fluorescent reporter behind the endogenous MRP-7 promoter indicate that the transporter is expressed in DA neurons. These studies show for the first time that a multidrug resistance protein is expressed in DA neurons, and its expression inhibits MeHg-associated DA neuron pathology.
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影响因子：
3.3
作者：
Bortfeld, M;Rius, M;Keppler, D
通讯作者：
Keppler, D
影响因子：
3.8
作者：
Hasegawa, Koichi;Miwa, Satsuki;Miwa, Johji
通讯作者：
Miwa, Johji
DOI：
10.1016/j.reprotox.2012.10.001
发表时间：
2012-12
期刊：
Reproductive toxicology (Elmsford, N.Y.)
影响因子：
--
作者：
Bridges CC;Joshee L;Zalups RK
通讯作者：
Zalups RK
影响因子：
4.5
作者：
Guo, Bao-Qiang;Yan, Chong-Huai;Shen, Xiao-Ming
通讯作者：
Shen, Xiao-Ming
影响因子：
5.1
作者：
Della Torre, Camilla;Zaja, Roko;Corsi, Ilaria
通讯作者：
Corsi, Ilaria