Comparative in vitro and in vivo protein kinase C activation by selected pesticides and transition metal salts.
Various pesticides and transition metals induce oxidative deterioration of biological macromolecules. Protein kinase C (PKC) may mediate these effects. However, no information is available regarding whether these xenobiotics can modulate PKC which is a critical event signaling the increase in endothelial permeability and cell proliferation. Female Sprague-Dawley rats were treated p.o. with two 0.25 LD50 doses of selected pesticides and transition metal salts at 0 and 21 h, and killed at 24 h. PKC activities were measured in liver and brain tissues. Cultured PC-12 cells were incubated for 24 h with 50, 100 or 200 nM concentrations of these pesticides, while 0.20, 0.40 or 0.60 microM concentrations of cadmium chloride (Cd(II)) and sodium dichromate (Cr(VI)) salts were employed. PKC activations were observed in the hepatic and brain cytosol fractions by all xenobiotics. Approximately 1.4- to 2.0-fold and 1.6- to 3.5-fold increases in PKC activity in the hepatic and brain cytosol fractions were observed, respectively. In the hepatic tissues, the greatest increases in activities were observed with TCDD, chlorpyrifos, endrin and Cd(II), while chlorpyrifos and fenthion exerted the greatest increases in the brain tissues. In cultured PC-12 cells, the greatest activation of PKC was observed primarily with 100-nM concentrations of the pesticides. The maximum effects were induced by chlorpyrifos, fenthion, Cd(II) and Cr(VI) salt. The results clearly indicate that pesticides as well as Cd(II) and Cr(VI) salts can modulate a vital component of the cell signaling pathway, namely PKC activity. PKC may be a target of free radicals and oxidative stress, leading to altered cell proliferation and differentiation.
Bagchi
D
D
Department of Pharmaceutical and Administrative Sciences, Creighton University, Omaha, NE 68178, USA.
Bagchi
M
M
Tang
L
L
Stohs
S J
SJ
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D019256:Cadmium Chloride / Q000008:administration & dosage / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002840:Chromates / Q000008:administration & dosage / Q000633:toxicity; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006540:Herbicides / Q000008:administration & dosage / Q000633:toxicity*; D006843:Hydrocarbons, Chlorinated; D066298:In Vitro Techniques; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009946:Organothiophosphorus Compounds; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000633:toxicity; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
D002840:Chromates; D006540:Herbicides; D006843:Hydrocarbons, Chlorinated; D007306:Insecticides; D009946:Organothiophosphorus Compounds; D000072317:Polychlorinated Dibenzodioxins; C016104:sodium bichromate; D011493:Protein Kinase C; D019256:Cadmium Chloride