Paraquat-induced gene expression in rat kidney.
Paraquat, one of the most widely used herbicides, is highly toxic to humans and animals. There is much information regarding its toxic effects on the lungs, but less is known about its toxicity in other organs. Paraquat is thought to play pivotal roles in the pathophysiology of acute renal failure and the progression of chronic kidney disease. We investigated the effects of paraquat on gene expression in the kidneys of rats treated with paraquat using a DNA array system, and the gene up-regulation observed was confirmed by quantitative real-time RT-PCR. Rats were sacrificed at 3, 24 h after the first injection (20 mg/kg), and at 3 h after the second injection. Expression of six genes had increased significantly by 3 h after the first injection: metallothionein-1 (MT-1), phosphoenolpyruvate carboxykinase, Na/K-transporting ATPase beta1 subunit, glutamate oxaloacetic transaminase, glutathione-S-transferase, and heme oxygenase-1 (HO-1). The transcription levels of MT-1 and HO-1 showed the biggest increases, but the increases did not continue until 24 h after injection, and the second injection had less effect than the first. Up-regulation of MT-1 and HO-1 mRNA levels was confirmed at the protein level. We observed a paraquat-induced increase of these proteins at 3 h post-injection, whereas this level did not continue until 24 h, as observed in RNA levels. The MT-1 protein in kidneys had been consumed. In addition, the protein level due to the second injection did not increase to the same level as that due to the first injection. These results suggest that protection against paraquat injury is mediated by induction of expression of some genes, and suppression on the induction of MT-1 and HO-1 may explain the injury observed due to paraquat intake. This is the first report of inducible pathways of defense against paraquat-induced oxidative stress in the kidney.
Department of Medical Toxicology, Kawasaki Medical School, Kurashiki 701-0192, Japan. toxicology@med.kawasaki-m.ac.jp
Masafumi
M
Tomita
Toshiko
T
Okuyama
Hironobu
H
Katsuyama
Takaki
T
Ishikawa
D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D005982:Glutathione Transferase / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity*; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008668:Metallothionein / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010269:Paraquat / Q000633:toxicity*; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
D006540:Herbicides; C491055:Mt2A protein, rat; D012333:RNA, Messenger; D008668:Metallothionein; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D000254:Sodium-Potassium-Exchanging ATPase; D010269:Paraquat