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Transcriptomic analysis suggested the involvement of impaired lipid droplet biogenesis in graphene oxide-induced cytotoxicity in human umbilical vein endothelial cells.

Abstract：

:Previous studies revealed that direct contact with graphene oxide (GO) induced cytotoxic effects, but the importance of involvement of metabolic pathways, in particular lipid metabolism pathways, might be overlooked. In this study, human umbilical vein endothelial cells (HUVECs) were exposed to GO with large size (denoted as GO-L) or small size (denoted as GO-S), and transcriptomics were used to understand the mechanisms of cytotoxicity of GO at systemic levels. It was shown that GO-L more significantly induced cytotoxicity compared with GO-S. Transcriptomic analysis revealed that compared with GO-S, GO-L had larger impact on gene ontology terms related with mitochondrial function as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related with cell death and growth. But GO-S showed greater influence on KEGG pathways related with lipid metabolism. Both types of GO showed minimal impact on oxidative stress but increased de novo lipogenesis protein fatty acid synthase (FASN). However, only GO-S significantly promoted acyl-CoA synthetase 3 (ACSL3), a key enzyme responsible for esterification of free fatty acids and lipid droplet biogenesis. Not surprisingly, GO-L but not GO-S impaired lipid droplet biogenesis, and increasing lipid levels by oleic acid or α-linolenic acid reduced the cytotoxicity of GO-L to HUVECs. Combined, the results from this study suggested that impaired lipid droplet biogenesis was involved in GO-induced cytotoxicity in HUVECs, and inducing lipid droplet biogenesis could prevent the cytotoxicity of GO.

journal_name

Chem Biol Interact

journal_title

Chemico-biological interactions

authors

Luo Y,Wang X,Cao Y

doi

10.1016/j.cbi.2020.109325

subject

Has Abstract

pub_date

2021-01-05 00:00:00

pages

109325

eissn

0009-2797

issn

1872-7786

pii

S0009-2797(20)31828-7

journal_volume

333

pub_type

杂志文章

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