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 organs and tissues in the human body. Zinc is accumulated primarily in the mitochondria, where it is responsible for inhibition of mitochondrial aconitase activity, thereby increasing citrate production. The present study was designed 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 ZnCl(2) was analyzed by determination of phospholipid membrane asymmetry, nuclear fragmentation, DNA strand breaks, changes of mitochondrial potential and cellular pro/antiapoptotic proteins. Zinc induced apoptosis without involvement of p53 by decreasing mitochondrial transmembrane potential (DeltaPsi(m)) and Bcl-2 protein levels in proliferating epithelial cells. Thus, the high local concentrations of zinc ions in the prostatic lumen seem to be necessary to regulate proliferative activities and to enforce epithelial differentiation processes.
Untergasser
G
G
Institute for Biomedical Aging Research, Innsbruck, Austria.
Rumpold
H
H
Plas
E
E
Witkowski
M
M
Pfister
G
G
Berger
P
P
D000199:Actins / Q000378:metabolism; D017209:Apoptosis; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D010743:Phospholipids / Q000378:metabolism; D011467:Prostate / Q000166:cytology / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015032:Zinc / Q000502:physiology; D017967:Zinc Compounds / Q000494:pharmacology*
D000199:Actins; D002712:Chlorides; D008563:Membrane Lipids; D010743:Phospholipids; D019253:Proto-Oncogene Proteins c-bcl-2; D017967:Zinc Compounds; C016837:zinc chloride; D004247:DNA; D015032:Zinc