Mitochondrial dysfunction, perturbations of mitochondrial dynamics and biogenesis involved in endothelial injury induced by silica nanoparticles

As silica nanoparticles (SiNPs) pervade the global economy, emissions during the manufacturing, use, and disposal stages inevitably bring an environmental release, potentially result in harmful impacts. Endothelial dysfunction precedes cardiovascular disease, and is often accompanied by mitochondrial impairment and dysfunction. Endothelial dysfunction induced by SiNPs has been reported, however, the related mechanisms by which SiNPs interact with mitochondria are not well understood. In the present study, the authors examined SiNPs-induced mitochondrial dysfunction, and further demonstrated their adverse effects on mitochondrial dynamics and biogenesis in endothelial cells (HUVECs). Consequently, SiNPs entered mitochondria, caused mitochondrial swelling, cristae disruption and even disappearance. Further analyses revealed SiNPs increased the intracellular level of mitochondrial reactive oxygen species, eventually resulting in the collapse of mitochondrial membrane potential, impairments in ATP synthesis, cellular respiration and the activities of three ATP-dependent enzymes (including Na(+)/K(+)-ATPase, Ca(2+)-ATPase and Ca(2+)/Mg(2+)-ATPase), as well as an elevated intracellular calcium level. Furthermore, mitochondria in SiNPs-treated HUVECs displayed a fission phenotype. Accordingly, dysregulation of the key gene expressions (FIS1, DRP1, OPA1, Mfn1 and Mfn2) involved in fission/fusion event further certified the SiNPs-induced perturbation of mitochondrial dynamics. Meanwhile, SiNPs-treated HUVECs displayed declined levels of mitochondrial DNA copy number, PGC-1?, NRF1 and also TFAM, indicating an inhibition of mitochondrial biogenesis triggered by SiNPs via PGC-1?-NRF1-TFAM signalling. Overall, SiNPs triggered endothelial toxicity through mitochondria as target, including the induction of mitochondrial dysfunction, as well as the perturbations of their dynamics and biogenesis.

Authors: Guo C, Wang J, Jing L, Ma R, Liu X, Gao L, Cao L, Duan J, Zhou X, Li Y, Sun Z. ; Full Source: Environmental Pollution. 2017 Oct 24. pii: S0269-7491(17)32058-4. doi: 10.1016/j.envpol.2017.10.060. [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][Epub ahead of print][/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]