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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Hepatología bioquímica > DA - CIMA - Terapia génica y Hepatología - Hepatología bioquímica - Artículos de revista >

Identification of argininosuccinate lyase as a hypoxia-responsive gene in rat hepatocytes
Authors: Latasa, M.U. (María Ujué)
Carretero, M.V. (M. Victoria)
Garcia-Trevijano, E.R. (Elena R.)
Torres, L. (Luis)
Mato, J.M. (José María)
Avila, M.A. (Matías Antonio)
Keywords: Argininosuccinate lyase
Gene expression
Hypoxia
Liver
Issue Date: 2000
Publisher: Elsevier
Publisher version: http://www.sciencedirect.com/science/article/pii/S0168827800803001
ISSN: 0168-8278
Citation: Latasa MU, Carretero MV, Garcia-Trevijano ER, Torres L, Mato JM, Avila MA. Identification of argininosuccinate lyase as a hypoxia-responsive gene in rat hepatocytes. J Hepatol 2000 Nov;33(5):709-715.
Abstract
BACKGROUND/AIMS: The differential oxygenation of periportal and perivenous hepatocytes has been demonstrated as a major determinant in the zonated expression of certain metabolic pathways in the liver. We have searched for novel genes whose expression could be modulated by hypoxia in cultured rat hepatocytes. METHODS: Primary cultures of rat hepatocytes were incubated under normoxic (21% oxygen) or hypoxic (3% oxygen) conditions for 6 h. Differences in gene expression under both conditions were analyzed using the technique of differential display by means of PCR. RESULTS: We have identified the enzyme argininosuccinate lyase (ASL) as being downregulated by hypoxia. ASL is a cytosolic protein which participates in urea metabolism. ASL expression was time-dependently reduced in hypoxia. Hypoxia modulated the responses of this gene to the two main hormonal signals which induce ASL mRNA: glucocorticoids and cAMP. ASL mRNA levels decreased in response to ATP-reducing agents. CoCl2 mimicked the effect of hypoxia, suggesting the implication of a hemoprotein in this response. Hypoxia did not affect ASL mRNA stability, indicating that this effect occurs at the transcriptional level. CONCLUSIONS: Our observations suggest that differences in oxygen levels across the hepatic parenchyma could participate in the zonated expression of ASL.
Permanent link: http://hdl.handle.net/10171/23256
Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Hepatología bioquímica - Artículos de revista

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