c-Src-mediated activation of Erk1/2 is a reaction of epithelial cells to carbon nanoparticle treatment and may be a target for a molecular preventive strategy.
Owing to their specific physico/chemical properties, engineered as well as environmental nanoparticles can induce pathogenic endpoints in humans. Earlier studies demonstrated that pure carbon nanoparticles induce cell signaling events at the level of membrane receptor activation in lung epithelial cells. As a possible link between receptor activation and subsequent MAP-kinase signaling, the involvement of Src family kinases was investigated in cell lines of organs potentially exposed to environmental nanoparticles. Human cells from bronchus, intestine, and skin (keratinocytes) as well as rat lung epithelial cells showed similar time patterns for the activation of mitogen-activated protein kinases Erk1/2 as well as Src family kinases (SFK) when treated with carbon nanoparticles. Moreover, c-Src was identified as an integral part of the signaling mediating the transfer of information from membrane receptors to members of the proliferative signaling cascade in lung epithelial cells. Pretreatment of cells with the compatible solute ectoine, which is known to stabilize macromolecules, reduced the nanoparticle specific phosphorylation of SFK. Together with earlier in vivo and in vitro data, this demonstrates that compatible solutes prevent nanoparticle-induced signaling steps at the level of membrane-coupled signaling.
Peuschel
Henrike
H
Molekulare Toxikologie, Institut für Umweltmedizinische Forschung (IUF), Düsseldorf, Germany.
Sydlik
Ulrich
U
Haendeler
Judith
J
Büchner
Nicole
N
Stöckmann
Daniel
D
Kroker
Matthias
M
Wirth
Ragnhild
R
Brock
Winfried
W
Unfried
Klaus
K
D000599:Amino Acids, Diamino / Q000037:antagonists & inhibitors; D000818:Animals; D001980:Bronchi / Q000378:metabolism; D018938:Caco-2 Cells; D002244:Carbon / Q000633:toxicity; D003106:Colon / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity; D010766:Phosphorylation; D051381:Rats; D012867:Skin / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D000599:Amino Acids, Diamino; D002244:Carbon; C045628:ectoine; D066246:ErbB Receptors; D019061:src-Family Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3