Human glutathione dependent prostaglandin E synthase: gene structure and regulation

FEBS Letters

Thorén, Staffan¹  Jakobsson, Per-Johan¹  Leeb, Lisa²  Morgenstern, Ralf²  Forsberg, Lena² 

[1]Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden

[2]Institute of Environmental Medicine, Karolinska Institutet, S-171 77 Stockholm, Sweden

关键词: Prostaglandin;    PGE synthase;    MAPEG;    Gene;    Chromosomal;    Phenobarbital;    PGES;    prostaglandin E synthase;    PGD synthase;    prostaglandin D synthase;    MGST1;    microsomal glutathione transferase 1;    TCDD;    2;    3;    7;    8-tetrachlorodibenzo-p-dioxin;    PB;    phenobarbital;    AHR;    aryl hydrocarbon regulatory element;    COX;    cyclooxygenase;    MAPEG;    membrane associated proteins involved in eicosanoid and glutathione metabolism;    IL-1β;    interleukin-1β;   

DOI  :  10.1016/S0014-5793(00)01367-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A P1 clone containing the gene for human glutathione dependent PGE synthase (PGES) was isolated and characterized. The gene is divided into three exons, spans 14.8 kb and was localized to chromosome 9q34.3. In A549 cells, the protein and activity levels of PGES were increased by interleukin-1β. This increase was prevented by phenobarbital. Reporter constructs containing the 5′-flanking region of exon 1, which exhibited strong promoter activity, responded accordingly, except that interleukin-1β induced a transient increase followed by a decrease. As cyclooxygenase 2 expression has been reported to respond in a similar fashion, a transcriptional regulatory basis for the observed co-regulation with PGES is implied. The strong down-regulation by phenobarbital raises important issues concerning its mechanisms of action.

【 授权许可】

Unknown