Mechanisms of resistance to the cytotoxic effects of oxysterols in human leukemic cells.

We have developed hematopoietic cells resistant to the cytotoxic effects of oxysterols. Oxysterol-resistant HL60 cells were generated by continuous exposure to three different oxysterols-25-hydroxycholesterol (25-OHC), 7-beta-hydroxycholesterol (7beta-OHC) and 7-keto-cholesterol (7kappa-C). We investigated the effects of 25-OHC, 7beta-OHC, 7kappa-C and the apoptotic agent staurosporine on these cells.

Effect of oxysterols on hematopoietic progenitor cells.

Objectives: Oxysterols are hydroxylated derivatives of cholesterol detected in blood, cells, and tissues. They exhibit a number of biologic activities, including inhibition of cellular proliferation and cytotoxicity associated with induction of apoptosis. Given the important regulatory role of apoptosis in hematopoiesis, we investigated the effects of oxysterols on human hematopoietic progenitor cells (HPCs).

MERP1: a mammalian ependymin-related protein gene differentially expressed in hematopoietic cells.

We have utilized differential display polymerase chain reaction to investigate the gene expression of hematopoietic progenitor cells from adult bone marrow and umbilical cord blood. A differentially expressed gene was identified in CD34+ hematopoietic progenitor cells, with low expression in CD34- cells. We have obtained the full coding sequence of this gene which we designated human mammalian ependymin-related protein 1 (MERP1).