Biopolymers and cell. 2007; 23 (5): 391 - 397

Oxygen as a regulator of serine dehydratase (SerDH) gene expression

A. A. Samoylenko, N. N. Tepliuk, M. Yu. Obolenskaya, T. Kietzmann

An oxygen gradient is formed in the liver due to the unidirectional blood flow from the portal vein and hepatic artery to the central vein and due to the oxygen-consuming metabolic processes of the cells along the sinusoid. This gradient appears to be one of the major factors responsible for differential expression of a number of genes between periportal and perivenous zones of liver sinusoid. The serine dehydratase (SerDH) gene is predominantly expressed in the hepatocytes of periportal zone. Northern blot analysis and transfections with the SerDH promoter luciferase constructs containing SerDH promoter (-2303… +55 bp) upstream of the Firefly luciferase gene demonstrated that the SerDH expression was higher under normoxia (16% O₂) as compared to hypoxia (8% O₂). Four putative normoxia responsive elements (NRE) were found in the SerDH promoter (NRE-1, NRE-2, NRE-3, NRE-4). To identify which of these elements is functional in hepatocytes, several plasmids containing 6 copies of putative SerDH NRE’s upstream of the SV40 promoter and the Firefly luciferase gene were constructed. It was found that NRE-2 in both HeLa and HepG2 cells as well as NRE-1 in HeLa cells were responsible for the O₂-dependent SerDH gene expression.

Keywords: serine dehydratase gene, transcription regulation, reporter gene, luciferase, hepatocytes, normoxia.