CLUSTERIN GENE-EXPRESSION IN APOPTOTIC MDCK CELLS IS DEPENDENT ON THE APOPTOSIS-INDUCING STIMULUS

Clusterin (Apolipoprotein J, complement lysis inhibitor) is a widely expressed multifunctional glycoprotein. The expression of clusterin mRNA has been reported to be elevated in a broad spectrum of apoptotic or degenerative tissues. More recently, it was shown that within these tissues clusterin is expressed in the surviving rather than in the dying cells, and that clusterin gene expression is actually down-regulated in the apoptotic cells. We have studied the expression of the clusterin gene in apoptotic MDCK cells. Cell death was initiated by three different stimuli: application of the steroid hormone antagonist RU 486, activation of protein kinase C by the application of the phorbol ester TPA, and - since clusterin is involved in lipid and cholesterol transport - perturbation of cell membranes by cholesterol. We show that clusterin gene expression is repressed in cells undergoing apoptosis in response to the application of RU 486 and TPA, but is unchanged in cells in which apoptosis has been triggered by cholesterol treatment.