Mycotoxin fumonisin B1 alters cellular redox balance and signalling pathways in rat liver and kidney.
Mycotoxin fumonisin B(1) (FB(1)) is a frequent contaminant of grain, particularly maize, but the mechanism of its toxicity in the kidney and liver is not fully understood. FB(1)-stimulated oxidative stress might disturb cellular redox state and signal transduction pathways of the target cells. In this study we measured total intracellular glutathione (GSH), and assessed mitogen-activated protein kinases (MAPKs) activation and the expression of heat shock proteins (Hsps) Hsp25 and Hsp70 in the liver and kidney of male Wistar rats given 0.5 mg FB(1)/kg b.w. intraperitoneally for 2 or 7 days. The effect of FB(1) on GSH levels, MAPK activation and Hsp expression was found to be related to the type of tissue affected and the length of treatment. In rat liver, cellular GSH content increased, Hsp expression was up-regulated, and ERK and p38 were activated after the 7-day treatment, while even the 2-day treatment sufficed to produce phospho-JNK signal. In rat kidney, GSH levels decreased after the 2- and 7-day treatment with FB(1), while after the 7-day treatment all three MAPKs were activated, Hsp25 expression increased and Hsp70 expression decreased. In conclusion, FB(1) alters cellular redox balance, which leads to tissue-specific activation and expression of redox-sensitive signalling molecules. It seems that kidney cells are more sensitive to adverse effects of FB(1).
Rumora
Lada
L
Faculty of Pharmacy and Biochemistry, Department of Medical Biochemistry and Haematology, Domagojeva 2, 10000, Zagreb, Croatia.
Domijan
Ana-Marija
AM
Grubisić
Tihana Zanić
TZ
Peraica
Maja
M
D000818:Animals; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D037341:Fumonisins / Q000008:administration & dosage / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D007274:Injections, Intraperitoneal; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009183:Mycotoxins / Q000008:administration & dosage / Q000633:toxicity*; D009363:Neoplasm Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D037341:Fumonisins; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D009183:Mycotoxins; D009363:Neoplasm Proteins; C056933:fumonisin B1; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005978:Glutathione