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Am J Physiol Regul Integr Comp Physiol 291: R1295-R1302, 2006. First published June 22, 2006; doi:10.1152/ajpregu.00095.2006
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APPETITE, OBESITY, DIGESTION, AND METABOLISM

Downregulation in the expression of the serine dehydratase in the rat liver during chronic metabolic acidosis

Inmaculada López-Flores,1 Juan Peragón,1 Raquel Valderrama,1 Francisco J. Esteban,2 Francisco Luque,3 M. Ángeles Peinado,2 Fermín Aranda,1 José A. Lupiáñez,4 and Juan B. Barroso1

1Areas of Biochemistry and Molecular Biology, 2Cell Biology, and 3Genetics, Department of Experimental Biology, University of Jaén, Jaén, Spain; and 4Department of Biochemistry and Molecular Biology, Centre for Biological Sciences, University of Granada, Granada, Spain

Submitted 6 February 2006 ; accepted in final form 20 June 2006

Blood pH controls the activity of important regulatory enzymes in the metabolism. Serine dehydratase (SerDH) transforms L-serine into pyruvate and ammonium and is involved in the regulation of gluconeogenesis from serine in the rat liver. In this work, we investigate the effect of chronic metabolic acidosis on the kinetics, specific protein level, tissue location, and mRNA levels of rat liver SerDH. Experimental acidosis was induced in rats by ingestion of 0.28 M ammonium chloride solution for 10 days. Acidosis significantly (P < 0.05) decreased SerDH activity at all substrate concentrations assayed. Moreover, the Vmax value was 38.50 ± 3.51 mU/mg (n = 7) of mitochondrial protein in the acidotic rats and 92.49 ± 6.79 mU/mg (n = 7) in the control rats. Western blot analysis revealed a significant reduction (14%) in the level of SerDH protein content in the rat liver during acidosis. Immunohistochemical analysis showed that SerDH location did not change in response to chronic metabolic acidosis and confirmed previous results on SerDH protein levels. Moreover, the SerDH mRNA level, estimated by RT-PCR, was also significantly 33.8% lower than in control. These results suggest that during experimental acidosis a specific repression of rat-liver SerDH gene transcription could result, lowering the amount and activity of this enzyme. The changes found in SerDH expression are part of an overall metabolic response of liver to maintain acid-base homeostasis during acidosis.

NH4Cl; reverse transcriptase-polymerase chain reaction; serine catabolism



Address for reprint requests and other correspondence: Dr. J. Peragón, Área de Bioquímica y Biología Molecular, Departamento de Biología Experimental, Universidad de Jaén, Campus Las Lagunillas, 23071 Jaén, Spain (e-mail: jperagon{at}ujaen.es)







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