trans,trans-2,4-Decadienal induces endothelial cell injury by impairing mitochondrial function and autophagic flux

This study investigated the toxic effects of trans,trans-2,4-decadienal (tt-DDE) on vascular endothelial cells as well as the underlying mechanisms involved. Human umbilical vascular endothelial cells (HUVECs) were treated with different concentrations of tt-DDE for 24 h, and cell viability, colony formation ability, apoptosis, mitochondrial function and autophagy pathway were determined. The results showed that tt-DDE dose-dependently inhibited cell viability and colony formation, and increased lactate dehydrogenase (LDH) release and apoptosis in HUVECs. Besides, tt-DDE exposure induced extensive mitochondrial damage, as evidenced by the decreased mitochondrial DNA copy number, ATP synthesis, and mitochondrial membrane potential, and increased mitochondrial reactive oxygen species (ROS) production and cytochrome c release from mitochondria. tt-DDE also induced mitochondrial fragmentation and fission by increasing DNM1L protein expression and DNM1L mitochondrial translocation. Additionally, tt-DDE treatment resulted in the blockage of autophagic flux and accumulation of autophagosomes in endothelial cells. Further investigation revealed that the inhibition of autophagy by 3-methyladenine aggravated tt-DDE-induced mitochondrial dysfunction and cell injury. However, scavenging of ROS by N-acetyl-l-cysteine (NAC) significantly prevented tt-DDE-induced mitochondrial damage, autophagy dysfunction, and cell injury. These data indicated that tt-DDE induced endothelial cell injury through impairing mitochondrial function and autophagic flux.

Automated summary

This study found that tt-DDE induced endothelial cell injury by impairing mitochondrial function and autophagic flux. Scavenging of reactive oxygen species by N-acetyl-l-cysteine significantly prevented mitochondrial damage, autophagy dysfunction, and cell injury caused by tt-DDE exposure.