Plasma Mitochondrial Peptide Assays as Biomarkers of Environmental Toxin Exposure

血浆线粒体多肽作为环境毒素暴露生物标志物的研究 线粒体功能障碍与许多慢性病有关，而线粒体 大量环境毒素的靶标，但没有经过验证的循环标记可用 用于评估因环境暴露而导致的线粒体功能或功能障碍。 线粒体含有近千种源于细胞核的蛋白质，但线粒体 染色体只编码13种蛋白质。我们最近发现了一个新的线粒体家族 衍生多肽(MDP)。其中包括人素和我们命名的六个人素样肽。 SHLPs，在体外和体内有效地调节细胞的存活和代谢过程。我们 建议循环中的人蛋白和其他MDP的酶联免疫吸附试验是可靠的标记物 线粒体功能，可作为相关线粒体功能障碍的早期指标 对环境的侮辱。我们在这个项目中的目标包括持续发展和 人和小鼠体内人蛋白和SHLP的酶联免疫吸附试验的特征。我们的预赛 数据显示，在与以下疾病相关的人类疾病状态中，它们的水平异常 线粒体功能障碍和急性阿霉素暴露的小鼠。我们还将 检测线粒体毒素鱼藤酮和阿霉素对细胞株的体外作用 和原代培养对线粒体表达和生产的影响 多肽，并将其与线粒体功能的测量相关联。最后，我们将确定 血浆线粒体肽水平与线粒体功能障碍的关系 小鼠短期和长期暴露于线粒体毒素鱼藤酮和阿霉素 学习。我们将评估毒素暴露后MDP循环水平的变化，以及 将它们与牺牲动物体内这些多肽的器官特异性水平相关联，以及 线粒体功能的体内和体外分析。总之，这些研究将确立 循环线粒体肽测定作为线粒体功能障碍标志物的价值 由于环境毒素暴露而产生，并将为未来创建一套关键工具 监测暴露在这种毒素下的人类的研究。这将使预防和干预成为可能 处于与线粒体功能障碍相关的疾病的亚临床阶段。

Plasma Mitochondrial Peptide Assays as Biomarkers of Environmental Toxin Exposure Mitochondrial dysfunction is associated with a number of chronic diseases and mitochondria are a target for numerous environmental toxins, but no validated circulating markers are available for assessing mitochondrial function or dysfunction resulting from environmental exposures. Mitochondria contain nearly a thousand proteins of nuclear origin, but the mitochondrial chromosome only encodes 13 proteins. We recently identified a family of novel mitochondrial derived peptides (MDPs). These include humanin and six humanin-like peptides we named SHLPs, which potently regulate cell survival and metabolic processes in vitro and in vivo. We propose that ELISA assays for circulating humanin and other MDPs represent robust markers of mitochondrial function and will serve as early indicators of mitochondrial dysfunction associated with environmental insults. Our goals in this project include continued development and characterization of ELISA assays for humanin and SHLPs in humans and mice. Our preliminary data demonstrates abnormalities in their levels in human diseases states associated with mitochondrial dysfunction and in mice subjected to acute doxorubicin exposure. We will also examine the in vitro effects of the mitochondrial toxins Rotenone and Doxorubicin on cell lines and primary cultures in terms of their effect on the expression and production of mitochondrial peptides, and correlate this to measures of mitochondrial function. Finally we will determine the relationship between plasma levels of mitochondrial peptides and mitochondrial dysfunction, in mice exposed to the mitochondrial toxins Rotenone and Doxorubicin in short term and long-term studies. We will assess changes in circulating levels of MDPs following toxin exposure and correlated them to organ-specific levels of these peptides from sacrificed animals as well as to in vivo and ex vivo analysis of mitochondrial function. Together, these studies will establish the utility of circulating mitochondrial peptide assays as markers of mitochondrial dysfunction resulting from environmental toxin exposure and will create a critical set of tools for future studies to monitor humans exposed to such toxins. This will enable prevention and intervention in subclinical stages of diseases related to mitochondrial dysfunction.