Journal
LIFE SCIENCES
Volume 66, Issue 18, Pages PL265-PL270Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0024-3205(00)00500-2
Keywords
lipocortin 1; annexin I; apoptosis; U937 cells; transfection
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The potential involvement of endogenous lipocortin 1 in the process of cellular apoptosis, particularly in cells of the myelo-monocytic lineage, has been investigated. U937 cells were transfected either with an antisense or a sense DNA for Lipocortin 1 and the stable clones 36.4AS clone (20-40% lower Lipocortin 1 levels) and 15S (30% higher lipocortin 1 levels) were obtained. Cell apoptosis was induced by incubation with tumor necrosis factor-a: optimal responses were observed within a 24 h incubation period at a 5 ng/ml concentration. Apoptosis was assessed both morphologically, by annexin V binding and cell cycle analysis with propidium iodide. Whilst no consistent difference was seen between wild type cells and clone 36.4AS, a higher incidence of apoptosis (ranging from +30% to +60%) was observed in the 15S clone. Release of arachidonic acid from loaded cells was promoted by 24 h incubation with the cytokine, and a higher degree of release was measured in the 15S clone. These data indicate that endogenous intracellular lipocortin 1 is involved in the promotion of apoptosis in cells of the myelo-monocytic derivation. (C) 2000 Elsevier Science Inc.
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