Expression and specific activities of carbamoyl phosphate synthetase 1 in chronic hypoxic rats
Abstract: Urea biosynthesis is
a very important process in the liver which needs ATP, CO2 and functional
mitochondria or aerobic condition. Liver can adapt to hypoxic condition,
generally and locally. This study aimed to analyze the effect of chronic hypoxia
on liver urea biosynthesis as indicated by the level and specific activity of
mRNA of carbamoyl phosphate synthetase 1 (CPS1), a key enzyme in urea
biosynthesis in hypoxic rats.
Methods: 20 male Sprague-Dawley rats were placed in hypoxic chamber supplied
by a mixture of 10% O2 and 90% N2. Five rats were sacrificed at 1, 3, 5, and 7
days after exposure. Liver homogenates were analyzed for HIF-1 (hypoxia
inducible factor-1) by ELISA, CPS1 mRNA by real time RT-PCR and CPS1 enzymatic
specific activities by Pierson method. Data were analyzed by ANOVA test and
Pearson correlation.
Results: The HIF-1 in liver increased significantly, as well as CPS1 mRNA
and CPS1 enzymatic activities (p<0.05). There was a strong correlation
(r=0.618; p<0.01) between the level of CPS1 mRNA and CPS1 enzymatic
activities, moderate correlation between HIF-1 and CPS1 mRNA (r=0.419;
p<0.05) but no correlation between HIF-1 and CPS1 enzymatic activities. The
study indicated that urea biosynthesis in liver was affected by hypoxia and
partially under HIF-1 regulation. The study also found increase of urea and NH3
biosynthesis related to proteolysis as indicated by the decrease of total body
weight and liver weight.
Conclusion: There was an increase in the expression and specific activities
of CPS1 in urea biosynthesis as a result of increasing proteolysis in chronic hypoxic condition.
Author: Uly A. Nikmah, Ani R.
Prijanti, Sri W.A. Jusman, Mohamad Sadikin
Journal Code: jpkedokterangg160132