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http://purl.uniprot.org/citations/11097477http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/11097477http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
http://purl.uniprot.org/citations/11097477http://purl.org/dc/terms/identifier"doi:10.1016/s0168-8278(00)80300-1"xsd:string
http://purl.uniprot.org/citations/11097477http://purl.uniprot.org/core/author"Mato J.M."xsd:string
http://purl.uniprot.org/citations/11097477http://purl.uniprot.org/core/author"Avila M.A."xsd:string
http://purl.uniprot.org/citations/11097477http://purl.uniprot.org/core/author"Garcia-Trevijano E.R."xsd:string
http://purl.uniprot.org/citations/11097477http://purl.uniprot.org/core/author"Torres L."xsd:string
http://purl.uniprot.org/citations/11097477http://purl.uniprot.org/core/author"Latasa M.U."xsd:string
http://purl.uniprot.org/citations/11097477http://purl.uniprot.org/core/author"Carretero M.V."xsd:string
http://purl.uniprot.org/citations/11097477http://purl.uniprot.org/core/date"2000"xsd:gYear
http://purl.uniprot.org/citations/11097477http://purl.uniprot.org/core/name"J Hepatol"xsd:string
http://purl.uniprot.org/citations/11097477http://purl.uniprot.org/core/pages"709-715"xsd:string
http://purl.uniprot.org/citations/11097477http://purl.uniprot.org/core/title"Identification of argininosuccinate lyase as a hypoxia-responsive gene in rat hepatocytes."xsd:string
http://purl.uniprot.org/citations/11097477http://purl.uniprot.org/core/volume"33"xsd:string
http://purl.uniprot.org/citations/11097477http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/11097477
http://purl.uniprot.org/citations/11097477http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/11097477
http://purl.uniprot.org/uniprot/P20673#attribution-80F7D2206CB77AEF16FB436F9B567BDBhttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/11097477
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http://purl.uniprot.org/uniprot/#_P20673-mappedCitation-11097477http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/11097477
http://purl.uniprot.org/uniprot/P20673http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/11097477
http://purl.uniprot.org/uniprot/A0A8J8XG16http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/11097477
http://purl.uniprot.org/uniprot/A0A8I6AB44http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/11097477