From: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0038038
PLOS ONE
Kitaguchi Y, Taraseviciene-Stewart L, Hanaoka M, Natarajan R, Kraskauskas D, et al. (2012) Acrolein Induces Endoplasmic Reticulum Stress and Causes Airspace Enlargement. PLoS ONE 7(5): e38038. doi:10.1371/journal.pone.0038038
Acrolein Induces Endoplasmic Reticulum Stress and Causes Airspace Enlargement
The authors state, “Given the relative abundance and toxic potential of acrolein in inhaled cigarette smoke, it is surprising how little is known about the pulmonary and systemic effects of acrolein.”
According to the authors, “It has been long appreciated that cigarette smoke contains particles, volatile components, and endotoxin [7], [8] and that a multitude of individual smoke components, or interactions between a number of these components, are responsible for the chronic respiratory bronchiolitis [9] and emphysematous destruction [10] of the lung. Stedman reported 40 years ago that cigarette smoke is comprised of more than 4700 chemicals [11] and therefore many investigators consider it a somewhat futile exercise to investigate which of these cigarette smoke components cause inflammation and lung tissue damage. Although the burning cigarette may also be an antigen delivery device [10], there may be chemicals which, when inhaled, have cytotoxic and genotoxic effects. One such compound inhaled with the cigarette smoke is the highly aggressive aldehyde acrolein. Depending on the brand of the cigarette 200–400 µg of this volatile aldehyde are inhaled with the smoke generated by a single cigarette [12]. The ‘dosing’ of aldehyde to the lung is not restricted to the airways via inhalation, because acrolein also appears in the blood of smokers and is excreted in the urine [13]. Systemic effects of acrolein are likely also to occur following uptake via the gastrointestinal tract. Acrolein forms protein – and DNA-adducts [14]–[16] and it has been shown that acrolein affects membrane lipids [17]. Of interest, acrolein, like ceramide [18], [19], is also an endogenous metabolic product produced by activated neutrophils [20], [21]. Acrolein has been shown to induce the release of cytokines from human macrophages, and elevated plasma levels of acrolein can be measured as a byproduct of polyamine metabolism in patients with renal failure [22], [23].”
In their study, the authors found that “acute administration to acrolein induced ER [endoplasmic reticulum] stress response gene expression and upregulated VEGF [vascular endothelial growth factor] protein in the lung tissue. The chronic exposure to acrolein caused apoptosis [process of programmed cell death] of alveolar septal cells, downregulation of VEGF protein expression, and the development of emphysema. There was a significant accumulation of acrolein-protein adducts in the lungs of COPD patients suggestive of a role of acrolein in emphysema pathogenesis.”
northpolecleanair 