title: Downregulation in the expression of the serine dehydratase in the rat liver during chronic metabolic acidosis.
abstract: 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.
authors.affiliation: Area de Bioquímica y Biología Molecular, Departamento de Biología Experimental, Universidad de Jaén, Campus Las Lagunillas, 23071 Jaén, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: López-Flores
authors.forename: Juan
authors.initials: J
authors.lastname: Peragón
authors.forename: Raquel
authors.initials: R
authors.lastname: Valderrama
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Esteban
authors.forename: Francisco
authors.initials: F
authors.lastname: Luque
authors.forename: M Angeles
authors.initials: MA
authors.lastname: Peinado
authors.forename: Fermín
authors.initials: F
authors.lastname: Aranda
authors.forename: José A
authors.initials: JA
authors.lastname: Lupiáñez
authors.forename: Juan B
authors.initials: JB
authors.lastname: Barroso
mesh_terms: D000136:Acid-Base Equilibrium / Q000502:physiology; D000138:Acidosis / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D012695:L-Serine Dehydratase / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012694:Serine / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D012694:Serine; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D012695:L-Serine Dehydratase