High levels of zinc ions induce loss of mitochondrial potential and degradation of antiapoptotic Bcl-2 protein in in vitro cultivated human prostate epithelial cells

Prostate epithelial cells contain the highest levels of zinc among all orga ns and tissues in the human body. Zinc is accumulated primarily in the mito chondria, where it is responsible for inhibition of mitochondrial aconitase activity, thereby increasing citrate production. The present study was des igned to clarify the role of zinc for human prostate epithelial cell growth and apoptosis. Apoptosis of in vitro cultivated human prostate epithelial cells exposed to ZnCl2 was analyzed by determination of phospholipid membra ne asymmetry, nuclear fragmentation, DNA strand breaks, changes of mitochon drial potential and cellular pro/antiapoptotic proteins. Zinc induced apopt osis without involvement of p53 by decreasing mitochondrial transmembrane p otential (Delta psi (m)) and Bcl-2 protein levels in proliferating epitheli al cells. Thus, the high local concentrations of zinc ions in the prostatic lumen seem to be necessary to regulate proliferative activities and to enf orce epithelial differentiation processes. (C) 2000 Academic Press.