TY - JOUR
T1 - Up-regulation of mRNA ventricular PRNP prion protein gene expression in air pollution highly exposed young urbanites
T2 - Endoplasmic reticulum stress, glucose regulated protein 78, and nanosized particles
AU - Villarreal-Calderon, Rodolfo
AU - Franco-Lira, Maricela
AU - González-Maciel, Angélica
AU - Reynoso-Robles, Rafael
AU - Harritt, Lou
AU - Pérez-Guillé, Beatriz
AU - Ferreira-Azevedo, Lara
AU - Drecktrah, Dan
AU - Zhu, Hongtu
AU - Sun, Qiang
AU - Torres-Jardón, Ricardo
AU - Aragón-Flores, Mariana
AU - Calderón-Garcidueñas, Ana
AU - Diaz, Philippe
AU - Calderón-Garcidueñas, Lilian
PY - 2013/11/28
Y1 - 2013/11/28
N2 - Mexico City Metropolitan Area children and young adults exposed to high concentrations of air pollutants including fine and ultrafine particulate matter (PM) vs. clean air controls, exhibit myocardial inflammation and inflammasome activation with a differential right and left ventricular expression of key inflammatory genes and inflammasomes. We investigated the mRNA expression levels of the prion protein gene PRNP, which plays an important role in the protection against oxidative stress and metal toxicity, and the glucose regulated protein 78, a key protein in endoplasmic reticulum (ER) stress signaling, in ventricular autopsy samples from 30 children and young adults age 19.97 ± 6.8 years with a lifetime of low (n:4) vs. high (n:26) air pollution exposures. Light microscopy and transmission electron microscopy studies were carried out in human ventricles, and electron microscopy studies were also done in 5 young, highly exposed Mexico City dogs. There was significant left ventricular PRNP and bi-ventricular GRP78 mRNA up-regulation in Mexico City young urbanites vs. controls. PRNP up-regulation in the left ventricle was significantly different from the right, p < 0.0001, and there was a strong left ventricular PRNP and GRP78 correlation (p = 0.0005). Marked abnormalities in capillary endothelial cells, numerous nanosized particles in myocardial ER and in abnormal mitochondria characterized the highly exposed ventricles. Early and sustained cardiac ER stress could result in detrimental irreversible consequences in urban children, and while highly complex systems maintain myocardial homeostasis, failure to compensate for chronic myocardial inflammation, oxidative and ER stress, and particles damaging myocardial organelles may prime the development of pathophysiological cardiovascular states in young urbanites. Nanosized PM could play a key cardiac myocyte toxicity role.
AB - Mexico City Metropolitan Area children and young adults exposed to high concentrations of air pollutants including fine and ultrafine particulate matter (PM) vs. clean air controls, exhibit myocardial inflammation and inflammasome activation with a differential right and left ventricular expression of key inflammatory genes and inflammasomes. We investigated the mRNA expression levels of the prion protein gene PRNP, which plays an important role in the protection against oxidative stress and metal toxicity, and the glucose regulated protein 78, a key protein in endoplasmic reticulum (ER) stress signaling, in ventricular autopsy samples from 30 children and young adults age 19.97 ± 6.8 years with a lifetime of low (n:4) vs. high (n:26) air pollution exposures. Light microscopy and transmission electron microscopy studies were carried out in human ventricles, and electron microscopy studies were also done in 5 young, highly exposed Mexico City dogs. There was significant left ventricular PRNP and bi-ventricular GRP78 mRNA up-regulation in Mexico City young urbanites vs. controls. PRNP up-regulation in the left ventricle was significantly different from the right, p < 0.0001, and there was a strong left ventricular PRNP and GRP78 correlation (p = 0.0005). Marked abnormalities in capillary endothelial cells, numerous nanosized particles in myocardial ER and in abnormal mitochondria characterized the highly exposed ventricles. Early and sustained cardiac ER stress could result in detrimental irreversible consequences in urban children, and while highly complex systems maintain myocardial homeostasis, failure to compensate for chronic myocardial inflammation, oxidative and ER stress, and particles damaging myocardial organelles may prime the development of pathophysiological cardiovascular states in young urbanites. Nanosized PM could play a key cardiac myocyte toxicity role.
KW - Air pollution
KW - BiP
KW - Children
KW - Endoplasmic reticulum stress
KW - GRP78
KW - Myocardial damage
KW - Nanoparticles
KW - Oxidative stress
KW - PRNP
KW - Particulate matter
KW - Sarcoplasmic reticulum
UR - http://www.scopus.com/inward/record.url?scp=84888598755&partnerID=8YFLogxK
U2 - 10.3390/ijms141223471
DO - 10.3390/ijms141223471
M3 - Article
C2 - 24287918
AN - SCOPUS:84888598755
SN - 1661-6596
VL - 14
SP - 23471
EP - 23491
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 12
ER -