Regulation of Cellular 5-Lipoxygenase Activity by Glutathione Peroxidases

Abstract

B-lymphocytes, monocytes, and partially differentiated human leukemic cell lines express 5-lipoxygenase protein but no concomitant cellular activity. Recently, we and others could show that glutathione peroxidases (GPx) are responsible for inhibition of 5-lipoxygenase activity in these cell lines [1,2]. Characterization of the endogenous 5-lipoxygenase inhibitors in the B-lymphocytic cell line BL41-E95A and in HL-60 cells demonstrated that the respective inhibitors display properties identical to GPx-4 [2]. Characterization of the functionality of this inhibitor revealed that inhibition of 5-lipoxygenase in these cell lines was abolished when 5-LO activity was determined in cell homogenates in the absence of thiols. In contrast to these findings, monocytic cells contain an endogenous inhibitor which suppresses 5-lipoxygenase activity in intact cells and in cell homogenates both in the presence and absence of thiols (Figure 1). Purification of this endogenous 5-LO inhibitor of monocytic cells followed by protein sequencing and immunoblotting revealed that the inhibitor is GPx-1. In contrast to peroxidase activity, there was no requirement for millimolar concentrations of thiols for 5-LO inhibition indicating that different catalytic properties of peroxidases are addressed by these two actions.