Gene-Regulated Release of Distinctive Volatile Organic Compounds from Stressed Living Cells

Abstract

Breath-borne volatile organic compounds (VOCs) have been increasingly studied as non-invasive biomarkers in both medical diagnosis and environmental health research. Recently, changes in breath-borne VOC fingerprints were demonstrated in rats and humans following pollutant exposures. In this study, the eukaryotic model Saccharomyces cerevisiae was used to study the release of cellular VOCs resulting from toxicant exposures (i.e., O3, H2O2, and CO2) and its underlying biological mechanism. Our results showed that different toxicant exposures caused the release of distinctive VOC profiles of yeast cells. The levels of ethyl acetate and ethyl n-propionate were altered in response to all the toxicants used in this study and could thus be targeted for future environmental toxicity monitoring. The RNA-seq results revealed significant changes in the metabolic or signaling pathways related to the ribosome, carbohydrate, and amino acid metabolisms after exposures. Notably, the shift from glycolysis to the pentose phosphate pathway of carbohydrate metabolism and the inhabitation of the aspartate pathway in the lysine synthesis was essential to the cellular antioxidation by providing reduced nicotinamide adenine dinucleotide phosphate (NADPH). The reprogrammed metabolisms could have resulted in the observed changes of VOCs released, e.g., the production of ethyl acetate for detoxification from yeast cells. This study provides further evidence that VOCs released from living organisms could be used to monitor and guard against toxic exposures while providing better mechanistic insights of the changes in breath-borne VOCs previously observed in rats and humans exposed to air toxicants.

Exhaled VOC Biomarkers from Rats Injected with PMs from Thirty-One Major Cities in China

“…Several studies have reported the detection of various aldehydes, such as acetaldehyde, heptanal, hexanal, nonanal, and octanal, in the exhaled breath of patients with various diseases, suggesting their potential as biomarkers for disease diagnosis. 20,23,49,50 Our findings indicate a persistent increase in pentanal, hexanal-M, hexanal-D, heptanal-M, and (E)-2-hexenal in the exhaled VOCs of rats exposed to PMSF for 6 days. This observation suggests that the body may have undergone pathological changes, potentially linked to the incomplete degradation of fatty acids.…”

“…Molecular Mechanism behind Exhaled VOC Profiles of Rats. Through literature research and the KEGG pathway analysis, 23,28,29,43,44 we identified the molecular mechanisms behind 13 biomarkers of exhaled VOCs (Figure 5). We found that the citrate cycle (TCA cycle), the fundamental metabolic pathway for the breakdown of carbohydrates, fats, and proteins in cell mitochondria, 45,46 is closely related to the production of ketones (hydroxyacetone and acetone), acids (acetic acid and lactate), and alcohols (1-propanol and butan-1-ol) in exhaled VOCs.…”

“…20−22 Exhaled long-chain aldehyde compounds, such as pentanal, hexanal, octanal, and nonanal, are considered potential biomarkers for lung cancer. 23,24 Our previous studies demonstrated notable alterations in the VOCs released by cells, rats, and populations in response to exposures to various pollutants. 25−27 In addition, aldehydes and their derivatives in VOCs are also found as important bioindicators.…”

“…Exhaled breath has been increasingly used to study disease, and it could offer significant insights into the processes preceding the health effects induced by PM exposure . Due to the diverse metabolic products originating from multiple signal pathways in the body, breath-borne volatile organic compounds (VOCs), particularly, have emerged as promising biomarkers for various fields, including early prevention, clinical decision-making for medical interventions, and COVID-19 screening. − Various technologies, including electrochemical sensors, electronic noses, photonic nose technologies, gas mass spectrometry, and ion mobility spectrometry, have been developed to enable accurate detection of these breath-borne VOC biomarkers. − Exhaled long-chain aldehyde compounds, such as pentanal, hexanal, octanal, and nonanal, are considered potential biomarkers for lung cancer. , Our previous studies demonstrated notable alterations in the VOCs released by cells, rats, and populations in response to exposures to various pollutants. − In addition, aldehydes and their derivatives in VOCs are also found as important bioindicators. They reflect strong oxidative stress and are indicative of the specific tissue composition and metabolism associated with tumors. , However, there have been no reports related to changes in breath-borne VOCs resulting from exposure to PMs.…”