title: Pulmonary exposure of rats to ultrafine titanium dioxide enhances cardiac protein phosphorylation and substance P synthesis in nodose ganglia.
abstract: The inhalation of engineered nanoparticles stimulates the development of atherosclerosis and impairs vascular function. However, the cardiac effects of inhaled engineered nanoparticles are unknown. Here, we investigate the effects of ultrafine titanium dioxide (UFTiO(2)) on the heart, and we define the possible mechanisms underlying the measured effects. Pulmonary exposure of rats to UFTiO(2) increased the phosphorylation levels of p38 mitogen-activated protein kinase and cardiac troponin I, but not Akt, in the heart and substance P synthesis in nodose ganglia. Circulatory levels of pro-inflammatory cytokines, and blood cell counts and differentials were not significantly changed after pulmonary exposure. Separately, the incubation of cardiac myocytes isolated from naïve adult rat hearts in vitro with UFTiO(2) did not alter the phosphorylation status of the same cardiac proteins. In conclusion, the inhalation of UFTiO(2) enhanced the phosphorylation levels of cardiac proteins. Such responses are likely independent of systemic inflammation, but may involve a lung-neuron-regulated pathway.
authors: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA. hvn4@cdc.gov
authors: Hong
authors: H
authors: Kan
authors: Zhongxin
authors: Z
authors: Wu
authors: Shih-Houng
authors: SH
authors: Young
authors: Teh-Hsun
authors: TH
authors: Chen
authors: Jared L
authors: JL
authors: Cumpston
authors: Fei
authors: F
authors: Chen
authors: Michael L
authors: ML
authors: Kashon
authors: Vincent
authors: V
authors: Castranova
mesh_terms: D000280:Administration, Inhalation; D000704:Analysis of Variance; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D019570:Inhalation Exposure; D007958:Leukocyte Count; D008856:Microscopy, Fluorescence; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D009620:Nodose Ganglion / Q000187:drug effects* / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000378:metabolism*; D014025:Titanium / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D016207:Cytokines; C009495:titanium dioxide; D013373:Substance P; D014025:Titanium