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多壁碳纳米管暴露的 HepG2 细胞中的脂质积累:可能的脂噬途径作用。

Lipid accumulation in multi-walled carbon nanotube-exposed HepG2 cells: Possible role of lipophagy pathway.

机构信息

Key Laboratory of Environment-Friendly Chemistry and Applications of Ministry Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan 411105, PR China.

Key Laboratory of Environment-Friendly Chemistry and Applications of Ministry Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan 411105, PR China; Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha 410205, PR China.

出版信息

Food Chem Toxicol. 2018 Nov;121:65-71. doi: 10.1016/j.fct.2018.08.033. Epub 2018 Aug 21.

Abstract

Nanoparticle (NP) exposure might promote hepatic steatosis, but relatively few studies investigated the influence of multi-walled carbon nanotubes (MWCNTs) on lipid accumulation in hepatocytes in vitro. This study investigated lipid accumulation and the possible role of lipophagy (autophagic degradation of lipid droplets) in MWCNT-exposed HepG2 cells. Pristine (XFM19) and carboxylated MWCNTs (XFM21) were internalized, accompanying cytotoxicity, lysosomal destabilization, and intracellular reactive oxygen species (ROS) production. Compared with XFM21, XFM19 promoted lipid accumulation in HepG2 cells more effectively, which was further enhanced by pre-incubation with autophagy inhibitor NHCl. In addition, MWCNTs increased the expression of lipophagy genes PLIN2 and BECN1 but decreased that of ATG7. The expression of endoplasmic reticulum (ER) stress regulators, namely DDIT3, HSPA5, and XBP-1s, was also altered in MWCNT exposed HepG2 cells. Combined, these results suggested that MWCNT exposure might promote lipid accumulation in hepatocytes probably through the modulation of lipophagy pathway.

摘要

纳米颗粒 (NP) 暴露可能会促进肝脂肪变性,但很少有研究调查多壁碳纳米管 (MWCNTs) 对体外肝细胞中脂质积累的影响。本研究调查了 MWCNT 暴露的 HepG2 细胞中的脂质积累和可能的自噬作用(脂质滴的自噬降解)的作用。原始(XFM19)和羧基化 MWCNTs(XFM21)被内化,伴随细胞毒性、溶酶体不稳定和细胞内活性氧 (ROS) 产生。与 XFM21 相比,XFM19 更有效地促进 HepG2 细胞中的脂质积累,而用自噬抑制剂 NHCl 预先孵育则进一步增强了这种作用。此外,MWCNTs 增加了自噬基因 PLIN2 和 BECN1 的表达,但降低了 ATG7 的表达。MWCNT 暴露的 HepG2 细胞中内质网 (ER) 应激调节剂,即 DDIT3、HSPA5 和 XBP-1s 的表达也发生了改变。综合这些结果表明,MWCNT 暴露可能通过调节自噬途径促进肝细胞中的脂质积累。

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