Department of Pediatrics
Cell Differentiation; Dimethylformamide; Enzyme Induction; Gene Expression Regulation, Neoplastic; Glutathione Peroxidase; Granulocytes; Humans; Leukemia, Myeloid; Leukemia, Promyelocytic, Acute; Membrane Glycoproteins; Monocytes; *NADPH Oxidase; Neoplasm Proteins; Phagocytes; RNA, Messenger; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured
Medical Cell Biology | Medical Genetics | Oncology | Pediatrics
We have used the HL-60 and PLB-985 myeloid leukemia cell lines to examine the regulation of expression of the important intracellular antioxidant enzyme, glutathione peroxidase (GSH-Px), during phagocytic cell differentiation in vitro. Induction of differentiation along the monocytic pathway by phorbol ester results in an approximately twofold rise in enzyme activity and a parallel increase in the rate of 75Se incorporation into immunoprecipitable GSH-Px protein. Induction along the granulocytic pathway by dimethyl formamide (DMF) results in similar changes in steady-state enzyme levels and rates of GSH-Px protein synthesis. Steady-state levels of GSH-Px gene transcripts also increase more than twofold, approximately in parallel with the enzyme levels. Nuclear run-on transcription assays of GSH-Px mRNA synthesis show ratios of induced to uninduced transcript levels of 2.24 and 1.59 with phorbol myristate acetate (PMA) induction and DMF, respectively, in HL-60 cells, and ratios of 1.34 and 3.46 with PMA and DMF, respectively, in PLB-985 cells. Half lives of GSH-Px mRNA are unchanged or slightly shorter after differentiation of HL-60 cells, and slightly longer after induction of PLB-985. Overall, the present studies show that GSH-Px activity rises during in vitro-induced monocytic or granulocytic differentiation of myeloid cell lines and that the increased expression of the cellular GSH-Px gene occurs through complex mechanisms that include transcriptional up-regulation. This pattern contrasts with the nearly complete cotranslational regulation of GSH-Px expression by exogenous selenium.
Blood. 1994 Dec 1;84(11):3902-8.
Shen Q, Chada S, Whitney C, Newburger PE. (1994). Regulation of the human cellular glutathione peroxidase gene during in vitro myeloid and monocytic differentiation. Open Access Publications by UMass Chan Authors. Retrieved from https://escholarship.umassmed.edu/oapubs/295