Cr (VI) increases tyrosine phosphorylation through reactive oxygen species-mediated reactions.
While Cr (VI)-containing compounds are well established carcinogens, the mechanisms of their action remain to be investigated. In this study we show that Cr (VI) causes increased tyrosine phosphorylation in human lung epithelial A549 cells in a time-dependent manner. N-acetyl-cysteine (NAC), a general antioxidant, inhibited Cr (VI)-induced tyrosine phosphorylation. Catalase, a scavenger of H2O2, sodium formate and aspirin, scavengers of hydroxyl radical (*OH), also inhibited the increased tyrosine phosphorylation induced by Cr (VI). SOD, an inhibitor of superoxide radical (O2*-), caused less inhibition. ESR study shows that incubation of Cr (VI) with the A549 cells generates *OH radical. The generation of radical was decreased by addition of catalase and sodium formate, while SOD did not have any inhibitory effect. Oxygen consumption measurements show that addition of Cr (VI) to A549 cells resulted in enhanced molecular oxygen consumption. These results indicate that Cr (VI) can induce an increase in tyrosine phosphorylation. H2O2 and *OH radicals generated during the process are responsible for the increased tyrosine phosphorylation induced by Cr (VI).
Qian
Y
Y
Cancer Center and Department of Microbiology and Immunology, School of Medicine, West Virginia University, Morgantown 26506, USA.
Jiang
B H
BH
Flynn
D C
DC
Leonard
S S
SS
Wang
S
S
Zhang
Z
Z
Ye
J
J
Chen
F
F
Wang
L
L
Shi
X
X
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002460:Cell Line; D002857:Chromium / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D005561:Formates / Q000494:pharmacology; D006490:Hemostatics / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D017665:Hydroxyl Radical / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005561:Formates; D006490:Hemostatics; D002857:Chromium; C030544:formic acid; C074702:chromium hexavalent ion; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D002374:Catalase; D011505:Protein-Tyrosine Kinases; D001241:Aspirin