Abstract
Compelling evidence suggests that volatile organic compounds (VOCs) have potentially harmful effects to the skin. However, knowledge about cellular signaling events and toxicity subsequent to VOC exposure to human skin cells is still poorly documented. The aim of this study was to focus on the interaction between 5 different VOCs (hexane, toluene, acetaldehyde, formaldehyde and acetone) at doses mimicking chronic low level environmental exposure and the effect on human keratinocytes to get better insight into VOC-cell interactions. We provide evidence that the proteasome, a major intracellular proteolytic system which is involved in a broad array of processes such as cell cycle, apoptosis, transcription, DNA repair, protein quality control and antigen presentation, is a VOC target. Proteasome inactivation after VOC exposure is accompanied by apoptosis, DNA damage and protein oxidation. Lon protease, which degrades oxidized, dysfunctional, and misfolded proteins in the mitochondria is also a VOC target. Using human skin explants we found that VOCs prevent cell proliferation and also inhibit proteasome activity in vivo. Taken together, our findings provide insight into potential mechanisms of VOC-induced proteasome inactivation and the cellular consequences of these events.
Highlights
At the interface between the body and the environment, the skin is directly exposed to chemical oxidants, air pollutants all of which are potent inducers of reactive oxygen species (ROS)[1, 2]
These findings suggest that protein quality control systems may be vulnerable to inactivation in conditions associated with Volatile organic compounds (VOCs) exposure resulting in accumulation of oxidatively modified proteins, mitochondrial dysfunction and cell death
These results demonstrate that the most significant change in cellular viability is caused by formaldehyde and acetaldehyde and little from the mixture of the 5 VOCs
Summary
At the interface between the body and the environment, the skin is directly exposed to chemical oxidants, air pollutants all of which are potent inducers of reactive oxygen species (ROS)[1, 2]. To study the effects of air pollutants with an in vitro model of human skin explants, new tools have to be developed using an air-liquid interface aimed at closely mimicking the physiological environment. Our results demonstrate that VOC exposure induced a significant decline in proteasome activity This is accompanied by reduction in cell viability, apoptosis, accumulation of oxidatively modified protein, DNA damage and mitochondria dysfunction. Our results demonstrated that exposure of keratinocytes to VOCs induced a significant decline in Lon protease activity, the protease in charge of protein degradation in the mitochondria. This was accompanied by mitochondrial ROS production. These findings suggest that protein quality control systems may be vulnerable to inactivation in conditions associated with VOC exposure resulting in accumulation of oxidatively modified proteins, mitochondrial dysfunction and cell death
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