Abstract
Outdoor particulate matter (PM10) exposure is carcinogenic to humans. The cellular mechanism by which PM10 is associated specifically with lung cancer includes oxidative stress and damage to proteins, lipids, and DNA in the absence of apoptosis, suggesting that PM10 induces cellular survival. We aimed to evaluate the PI3K/AKT/FoxO3a pathway as a mechanism of cell survival in lung epithelial A549 cells exposed to PM10 that were subsequently challenged with hydrogen peroxide (H2O2). Our results showed that pre-exposure to PM10 followed by H2O2, as a second oxidant stimulus increased the phosphorylation rate of pAKTSer473, pAKTThr308, and pFoxO3aSer253 2.5-fold, 1.8-fold, and 1.2-fold, respectively. Levels of catalase and p27kip1, which are targets of the PIK3/AKT/FoxO3a pathway, decreased 38.1% and 62.7%, respectively. None of these changes had an influence on apoptosis; however, the inhibition of PI3K using the LY294002 compound revealed that the PI3K/AKT/FoxO3a pathway was involved in apoptosis evasion. We conclude that nontoxic PM10 exposure predisposes lung epithelial cell cultures to evade apoptosis through the PI3K/AKT/FoxO3a pathway when cells are treated with a second oxidant stimulus.
Highlights
Air pollution is a problem that mainly affects large cities
Using a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002), we demonstrated that PM10 induced AKT phosphorylation and activation, preventing apoptosis in lung epithelial cells, with PI3K playing a critical role in the upregulation of the AKT/factor box O3a (FoxO3a) pathway under this context
Cell cultures were exposed to PM10 (10 μg/cm2), H2O2 (500 μM), or LY294002 (LY) inhibitor (50 μM), and we found that none of the concentrations tested had influence on cell viability (Table 1)
Summary
Air pollution is a problem that mainly affects large cities. It was estimated that in 2016 air pollution was responsible for 4,200,000 premature deaths [1]. Outdoor particulate matter with aerodynamic size ≤ 10 μm (PM10) is an important component of air pollution. It is a complex mixture of organic and inorganic compounds, including metals and polycyclic aromatic hydrocarbons, among others. PM10 is deposited in the upper respiratory tract, and epidemiological studies have shown PM-induced adverse effects on health such as chronic obstructive pulmonary disease, asthma, fibrosis, and lung cancer. An increase of 10 mg/m3 of PM2.5 and PM10 was associated with an increase of 8% and 3.4–6% in cancer mortality, respectively [2,3]. Since 2013, PM10 has been catalogued as carcinogenic to humans according to the International Agency for Research in Cancer (IARC) [4]
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