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Changes of renal mRNA species abundance by ochratoxin A
Abstract:
Ochratoxin A is a nephrotoxin produced by certain species of Aspergillus and Penicillium. We have found previously that renal but not hepatic P-enolpyruvate carboxykinase, and the mRNA for this enzyme, are rapidly decreased in rats and swine fed 0.1 to 1 mg/kg body weight for a few days. In the present study, we isolated kidney mRNA from rats fed ochratoxin A for 2-5 days. By screening a rat kidney cDNA library with [32P]RNA, we have identified several renal mRNAs whose concentration is changed within 2 days by the toxin. The transcription rate of each mRNA was measured in nuclei isolated from kidneys of rats fed ochratoxin A. The incorporation of [32P]UMP into P-enolpyruvate carboxykinase mRNA and the synthesis of other RNAs were not affected. Therefore, the toxin changes mRNA abundance at the post-transcriptional level.
Insights
Ochratoxin A, a kidney toxin, reduces specific mRNA levels in rats. This occurs post-transcriptionally, affecting mRNA abundance without altering gene transcription rates.
Area of Science:
- Toxicology
- Molecular Biology
- Biochemistry
Background:
- Ochratoxin A (OA) is a mycotoxin produced by Aspergillus and Penicillium species.
- OA is known to be nephrotoxic, affecting kidney function.
- Previous studies indicated OA decreases renal phosphoenolpyruvate carboxykinase (PEPCK) mRNA levels in rats and swine.
Purpose of the Study:
- To investigate the mechanism by which Ochratoxin A affects renal mRNA levels.
- To determine if OA alters mRNA abundance at the transcriptional or post-transcriptional level.
Main Methods:
- Rats were fed Ochratoxin A at doses of 0.1 to 1 mg/kg body weight for 2-5 days.
- Kidney mRNA was isolated and screened using a rat kidney cDNA library.
- [32P]RNA was used as a probe to identify changes in mRNA concentration.
- Nuclear transcription rates were measured to assess mRNA synthesis.
Main Results:
- Ochratoxin A exposure led to changes in the concentration of several renal mRNAs within 2 days.
- The transcription rate of phosphoenolpyruvate carboxykinase mRNA and other RNAs remained unaffected by OA.
- OA did not alter the synthesis of these specific mRNAs.
Conclusions:
- Ochratoxin A alters renal mRNA abundance at the post-transcriptional level.
- The toxin's effect on mRNA levels is not due to changes in gene transcription.
- This finding provides insight into the molecular mechanisms of Ochratoxin A nephrotoxicity.