From: http://ehp.niehs.nih.gov/1306911/
Environmental Health Perspectives, Volume 122, Issue 9, September 2014
Jun-Ho Jang, Shannon Bruse, Salam Huneidi, Ronald M. Schrader, Martha M. Monick, Yong Lin, A. Brent Carter,Aloysius J. Klingelhutz, and Toru Nyunoya
Acrolein-Exposed Normal Human Lung Fibroblasts in Vitro: Cellular Senescence, Enhanced Telomere Erosion, and Degradation of Werner’s Syndrome Protein
In the introduction to this article, the authors state: “Acrolein (2,3-propenal) is a reactive aldehyde used in the chemical industry for synthesis of organic compounds, in the production of methionine, and in methyl chloride refrigerant. Acrolein can be formed by incomplete combustion of gasoline, wood, plastic, tobacco products, diesel fuel, and paraffin wax and by heating cooking oil to high temperatures (Stevens and Maier 2008). Acrolein can be also generated as a product of endogenous threonine metabolism (mediated by myeloperoxidase) and/or spermine metabolism (mediated by amide oxidase) (Esterbauer et al. 1991; Faroon et al. 2008;Stevens and Maier 2008). Although acrolein is ubiquitously present in the environment, acrolein exposure through inhalation of cigarette smoke or smoke from burning of plastic or wood is generally considered to compose a large proportion of total human exposure. During inhalation of environmental tobacco smoke or cigarette smoke, the concentrations of acrolein at the airway surface can be as high as 80 μM (Eiserich et al. 1995). Acrolein rapidly penetrates cell membranes and induces oxidative stress and cytotoxicity through depletion of reductive glutathione (GSH) and inhibition of glutathione S-transferase (Kehrer and Biswal 2000; Li L et al. 2008; Nunoshiba and Yamamoto 1999; van Iersel et al. 1997). Acrolein (> 10 μM) can cause cell apoptosis or necrosis in various types of cultured respiratory cells, such as alveolar macrophages (Li et al. 1997), alveolar epithelial cells (Roy et al. 2009), and lung fibroblasts (Jia et al. 2009). The toxicity of acrolein is likely dependent on the cell type, redox balance, acrolein concentration, and duration of exposure.”
The authors conclude, “In the present study, we found that acrolein induced cellular senescence accompanied by activation of the p53–p21 pathway and proteasome-mediated WRN protein degradation in normal human lung fibroblasts (NHLF). siRNA (small interfering RNA)–mediated supression of p53 attenuated the effects of acrolein. Acrolein also enhanced telomere attrition. These data suggest that acrolein induces p53-mediated cellular senescence [“loss of a cell’s power of division and growth”] associated with telomere erosion and WRN protein instability.”
From: http://ghr.nlm.nih.gov/
National Institues of Health, National Medical Library, Genetics Home Reference
Apoptosis – “cell death, programmed; gene-directed cell death.” http://ghr.nlm.nih.gov/glossary=apoptosis
Necrosis – “A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death.” http://ghr.nlm.nih.gov/glossary=necrosis
Telomere – “The segment at the end of each chromosome arm which consists of a series of repeated DNA sequences that regulate chromosomal replication at each cell division. Some of the telomere is lost each time a cell divides, and eventually, when the telomere is gone, the cell dies.” http://ghr.nlm.nih.gov/glossary=telomere
WRN Protein – “WRN gene provides instructions for producing the Werner protein, which plays a critical role in repairing damaged DNA.” http://ghr.nlm.nih.gov/gene/WRN
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