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Laparotomy causes a transient induction of rat liver serine dehydratase mRNA
1Department of Biochemistry, Toyama Medical and Pharmaceutical University Faculty of Medicine, Japan.
Abstract:
Rat liver serine dehydratase mRNA shows rhythmicity with a high level at the onset of dark (19:00) and a low level at the onset of light (07:00). We have examined the effect of stress (laparotomy) on the rhythm. Upon laparotomy at 09:00 or 17:00, a marked induction of serine dehydratase mRNA occurred 2 h after operation. The elevated mRNA level then decreased and the original mRNA rhythm resumed 2 days later. By contrast, the transcription activator protein DBP mRNA level which shows a similar oscillation was not affected by this treatment. The induction was also seen in adrenalectomized rats that had been treated with hydrocortisone but not with saline or noradrenaline, indicating that glucocorticoids are absolutely necessary for the induction. Pretreatment of rats with phenoxybenzamine, and prazosin prevented the effect of laparotomy, but propranolol and yohimbine had no effect, indicating the necessity of the alpha 1-adrenergic stimulation for the induction. These results suggest that laparotomy releases glucocorticoids and neural noradrenaline that stimulates alpha 1-adrenergic receptors, thereby leading to the serine dehydratase gene expression.
Insights
Stress from surgery (laparotomy) significantly increases serine dehydratase mRNA in rats. This induction requires glucocorticoids and alpha 1-adrenergic stimulation, with normal rhythms returning within two days.
Area of Science:
- Biochemistry
- Molecular Biology
- Chronobiology
Background:
- Serine dehydratase mRNA in rat liver exhibits daily rhythmicity, peaking at dark onset and troughing at light onset.
- Stress responses can significantly impact gene expression and circadian rhythms.
Purpose of the Study:
- To investigate the effect of surgical stress (laparotomy) on the circadian rhythm of serine dehydratase mRNA in rat liver.
- To elucidate the molecular mechanisms underlying stress-induced alterations in serine dehydratase gene expression.
Main Methods:
- Laparotomy was performed on rats at different times of day to assess its impact on serine dehydratase mRNA levels.
- Analysis of mRNA levels for serine dehydratase and the transcription activator protein DBP.
- Experiments involving adrenalectomized rats treated with hydrocortisone, saline, or noradrenaline.
- Pharmacological interventions using alpha- and beta-adrenergic receptor antagonists (phenoxybenzamine, prazosin, propranolol, yohimbine).
Main Results:
- Laparotomy induced a marked increase in serine dehydratase mRNA levels 2 hours post-operation, irrespective of the time of day.
- The transcription activator protein DBP mRNA rhythm remained unaffected by laparotomy.
- Glucocorticoids were essential for the induction, as demonstrated in adrenalectomized rats.
- Alpha 1-adrenergic stimulation was necessary, as phenoxybenzamine and prazosin blocked the laparotomy-induced effect, while propranolol and yohimbine did not.
Conclusions:
- Surgical stress triggers a rapid induction of serine dehydratase gene expression in rat liver.
- The induction is mediated by a synergistic action of stress-released glucocorticoids and alpha 1-adrenergic receptor activation.
- This stress response pathway overrides the normal circadian regulation of serine dehydratase mRNA.