Park H-R, Oh R, Wagner P, Panganiban R, Lu Q
Program in Molecular and Integrative Physiological Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
Program in Molecular and Integrative Physiological Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
Int Rev Cell Mol Biol. 2017;331:55-82. doi: 10.1016/bs.ircmb.2016.10.001. Epub 2016 Nov 30.
Exposures to metal toxicants in the environment disrupt normal physiological functions and have been linked to the development of a myriad of human diseases. While the molecular and cellular mechanisms underlying metal toxicities remain to be fully understood, it is well appreciated that metal toxicants induce cellular stresses and that how cells respond to the stresses plays an important role in metal toxicity. In this review, we focus on how metal exposures induce stresses in the endoplasmic reticulum (ER) to elicit the unfolded protein response (UPR). We document the emerging evidence that induction of ER stress and UPR in the development of human diseases is associated with metal exposures. We also discuss the role of the interplay between ER stress and oxidative stress in metal toxicity. Finally, we review recent advances in functional genomics approaches and discuss how applications of these new tools could help elucidate the molecular mechanisms underlying cellular stresses induced by environmental metal toxicants.
环境中金属毒物的暴露会扰乱正常生理功能，并与多种人类疾病的发生有关。虽然金属毒性的分子和细胞机制仍有待充分了解，但人们普遍认识到金属毒物会诱导细胞应激，而细胞如何应对这些应激在金属毒性中起着重要作用。在本综述中，我们重点关注金属暴露如何在内质网（ER）中诱导应激以引发未折叠蛋白反应（UPR）。我们记录了新出现的证据，即内质网应激和未折叠蛋白反应在人类疾病发展过程中的诱导与金属暴露有关。我们还讨论了内质网应激和氧化应激之间的相互作用在金属毒性中的作用。最后，我们综述了功能基因组学方法的最新进展，并讨论了这些新工具的应用如何有助于阐明环境金属毒物诱导细胞应激的分子机制。
