Silica nanoparticles disrupt OPT-2/PEP-2-dependent trafficking of nutrient peptides in the intestinal epithelium
Silica nanoparticles disrupt OPT-2/PEP-2-dependent trafficking of nutrient peptides in the intestinal epithelium
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DOI：
10.1080/17435390.2019.1643048
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发表时间：
2019-08
期刊：
影响因子：
5
通讯作者：
A. Piechulek;L. Berwanger;A. von Mikecz
中科院分区：
文献类型：
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作者：
A. Piechulek;L. Berwanger;A. von Mikecz
摘要尽管二氧化硅纳米颗粒的应用越来越多，并确定口服暴露作为一个主要的入口，我们缺乏了解纳米二氧化硅在肠道中的作用。因此，我们研究了纳米二氧化硅与单个肠细胞的生物相互作用。选择无脊椎线虫秀丽隐杆线虫作为模式生物，其具有易处理的肠道和环境中纳米材料的现实靶生物。我们发现，纳米二氧化硅损害肠摄取的寡肽。在顶端OPT-2/PEP-2转运蛋白吸收的下游，二肽被捕获在异常囊泡中，这些囊泡随时间推移而生长，直径≥6 μm。肽囊泡不对应于已知的细胞器，如肠颗粒和形式独立于相关的基因产物GLO-1或GLO-3。异常肽囊泡的形成也独立于胰岛素/IGF-I受体（IGF-2）信号传导而发生，并且daf-2功能丧失突变体显示出特定的囊泡模式，包括沿单个肠细胞的顶膜沿着的不同定位。暴露C.由于线虫表现出生长减少和类似于OPT-2/PEP-2转运蛋白缺陷突变体的娇小表型，我们得出结论，纳米二氧化硅诱导的肽囊泡代表了一种新的二肽和三肽捕获区室，其破坏了营养肽的水解和代谢。
Abstract Despite of the increasing application of silica nanoparticles and identification of oral exposure as a major entry portal, we lack understanding of nanosilica effects in the gut. Thus, we investigated biointeractions of nanosilica with single intestinal cells. The invertebrate nematode Caenorhabditis elegans was chosen as model organism with a tractable intestine and realistic target organism of nanomaterials in the environment. We found that nanosilica impairs the intestinal uptake of oligopeptides. Downstream to absorption by the apical OPT-2/PEP-2 transporter dipeptides were trapped in aberrant vesicles that grow over time and reach diameters of ≥6 μm. The peptide vesicles do not correspond to known organelles such as gut granules and form independently of related gene products GLO-1 or GLO-3. Formation of aberrant peptide vesicles also occurred independently of insulin/IGF-I receptor (DAF-2) signaling and daf-2 loss of function mutants showed specific vesicle patterns including distinct localization along the apical membrane of single intestinal cells. As malnutrition of exposed C. elegans manifested in reduced growth and a petite phenotype similar to OPT-2/PEP-2 transporter deficient mutants, we conclude that nanosilica-induced peptide vesicles represent a new compartment of di- and tripeptide trapping which disrupts hydrolysis of nutrient peptides and metabolism.