DIFFERENTIAL EXPRESSION OF CLUSTERIN IN INDUCIBLE MODELS OF APOPTOSIS

Apoptosis (programmed cell death) and necrosis can be readily distinguished morphologically and biochemically. The most striking biochemical change observed in apoptotic cells is the cleavage of the genomic DNA into discrete nucleosome sized fragments, producing a laddering pattern when the DNA is examined electrophoretically. It has recently been shown that RNA and protein products of the testosterone-repressed prostate message-2 gene are induced, coordinate with the onset of cell death. This gene has been isolated from a variety of species and tissues, it is highly conserved, and collectively referred to as clusterin. We have examined a number of inducible leucocyte models of apoptosis, including glucocorticoid and calcium ionophore induced thymocyte death, 'aged' neutrophils and cytotoxic T cells, and found that in these situations that cell death is not associated with up-regulation of clusterin gene expression. The finding that clusterin is not expressed in all cells undergoing apoptosis would suggest that this molecule is not critical to the mechanism of cell death. It does, however, provide the first example of a readily detectable marker which is differentially expressed in cells undergoing apoptosis and adds further weight to the argument that apoptosis is not a uniform phenomena, but is dependent on the nature of the cells involved and the means of induction.