Airborne particulate matter (PM10) inhibits apoptosis through PI3K/AKT/FoxO3a pathway in lung epithelial cells: The role of a second oxidant stimulus
Por:
Garcia-Cuellar, Claudia M., Chirino, Yolanda I., Morales-Barcenas, Rocio, Soto-Reyes, Ernesto, Quintana-Belmares, Raul, Santibáñez-Andrade M., Sanchez-Perez, Yesennia
Publicada:
1 ene 2020
Resumen:
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. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Filiaciones:
Garcia-Cuellar, Claudia M.:
Instituto Nacional de Cancerología (INCan), Subdirección de Investigación Básica, San Fernando No. 22, Tlalpan, CDMX, 14080, Mexico
Inst Nacl Cancerol INCan, Subdirecc Invest Basica, San Fernando 22, Tlalpan 14080, Cdmx, Mexico
Chirino, Yolanda I.:
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Los Reyes Iztacala, Tlalnepantla, Estado de México CP 54090, Mexico
Univ Nacl Autonoma Mexico, Unidad Biomed, Fac Estudios Super Iztacala, Tlalnepantla 54090, Estado De Mexic, Mexico
Morales-Barcenas, Rocio:
Instituto Nacional de Cancerología (INCan), Subdirección de Investigación Básica, San Fernando No. 22, Tlalpan, CDMX, 14080, Mexico
Inst Nacl Cancerol INCan, Subdirecc Invest Basica, San Fernando 22, Tlalpan 14080, Cdmx, Mexico
Soto-Reyes, Ernesto:
Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana-Cuajimalpa, CDMX, CP 05300, Mexico
Univ Autonoma Metropolitana Cuajimalpa, Dept Ciencias Nat, Cdmx 05300, Mexico
Quintana-Belmares, Raul:
Instituto Nacional de Cancerología (INCan), Subdirección de Investigación Básica, San Fernando No. 22, Tlalpan, CDMX, 14080, Mexico
Inst Nacl Cancerol INCan, Subdirecc Invest Basica, San Fernando 22, Tlalpan 14080, Cdmx, Mexico
Santibáñez-Andrade M.:
Instituto Nacional de Cancerología (INCan), Subdirección de Investigación Básica, San Fernando No. 22, Tlalpan, CDMX, 14080, Mexico
Sanchez-Perez, Yesennia:
Instituto Nacional de Cancerología (INCan), Subdirección de Investigación Básica, San Fernando No. 22, Tlalpan, CDMX, 14080, Mexico
Inst Nacl Cancerol INCan, Subdirecc Invest Basica, San Fernando 22, Tlalpan 14080, Cdmx, Mexico
|