title: Up-regulation of mRNA ventricular PRNP prion protein gene expression in air pollution highly exposed young urbanites: endoplasmic reticulum stress, glucose regulated protein 78, and nanosized particles.
abstract: 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.
authors.affiliation: Davidson Honors College, University of Montana, Missoula, MT 59812, USA. lilian.calderon-garciduenas@umontana.edu.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Villarreal-Calderon
authors.forename: Maricela
authors.initials: M
authors.lastname: Franco-Lira
authors.forename: Angélica
authors.initials: A
authors.lastname: González-Maciel
authors.forename: Rafael
authors.initials: R
authors.lastname: Reynoso-Robles
authors.forename: Lou
authors.initials: L
authors.lastname: Harritt
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pérez-Guillé
authors.forename: Lara
authors.initials: L
authors.lastname: Ferreira-Azevedo
authors.forename: Dan
authors.initials: D
authors.lastname: Drecktrah
authors.forename: Hongtu
authors.initials: H
authors.lastname: Zhu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Sun
authors.forename: Ricardo
authors.initials: R
authors.lastname: Torres-Jardón
authors.forename: Mariana
authors.initials: M
authors.lastname: Aragón-Flores
authors.forename: Ana
authors.initials: A
authors.lastname: Calderón-Garcidueñas
authors.forename: Philippe
authors.initials: P
authors.lastname: Diaz
authors.forename: Lilian
authors.initials: L
authors.lastname: Calderón-Garcidueñas
mesh_terms: D000293:Adolescent; D000328:Adult; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D002648:Child; D004285:Dogs; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004912:Erythrocytes / Q000187:drug effects / Q000473:pathology; D005260:Female; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D052638:Particulate Matter / Q000032:analysis / Q000633:toxicity; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000393:Air Pollutants; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C512656:PRNP protein, human; D052638:Particulate Matter; D000072002:Prion Proteins; D011328:Prions; D012333:RNA, Messenger