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.
References: Oxidative damage and impairment of protein quality control systems in keratinocytes exposed to a volatile organic compounds cocktail. Dezest M, Le Bechec M, Chavatte L, Desauziers V, Chaput B, Grolleau JL, Descargues P, Nizard C, Schnebert S, Lacombe S, Bulteau AL. Sci Rep. 2017 Sep 6;7(1):10707. doi: 10.1038/s41598-017-11088-1.
*(A) Hematoxylin and eosin staining. NativeSkin models from a 30 year old donor female were cultured for 4 days with NativeSkin culture medium, exposed or not to VOCs (toluene, hexane, acetaldehyde, formaldehyde, acetone, 80 ppmV, each) for 4 hours every day. 24 hours after the last VOC exposure, samples were fixed in formalin and embedded in paraffin wax. 5 µm skin cross-sections were stained with hematoxylin eosin. Scale bar is 100 µm. (B) Apoptosis analysis. 5 µm skin cross-sections were immuno-stained for active caspase 3 to detect apoptotic cells. All pictures are representative of the whole sample. Scale bar is 100 µm.