A low-molecular-weight fraction of human seminal plasma activates adenylylcyclase and induces caspase 3-independent apoptosis in prostatic epithelial cells by decreasing mitochondrial potential and Bcl-2/Bax ratio

The majority of elderly men are affected by benign and malign diseases of t he prostate that are governed by endocrine factors and local stromal/epithe lial and luminal/epithelial interactions. Prostate epithelial cells secrete numerous factors into the seminal plasma (SMP) that are thought to be resp onsible for nutrition, accurate pH, and ionic environment of sperm. Our hyp othesis assumes that prostatic factors responsible for optimal fertility mi ght have retrograde influences on epithelial cell growth, differentiation, and function. SMP was analyzed for proteins and other biologically active s ubstances by size exclusion highperformance liquid chromatography. Each fra ction was investigated for its effect on cell growth and death. A low molec ular mass fraction (2-4 kDa) was responsible for inducing apoptosis in prol iferating prostate epithelial cells. Signal transduction was mediated by th e production of cAMP; no significant changes in tyrosine phosphorylation of membrane receptors were observed. Mechanisms of apoptosis, i.e., caspase- and mitochondria-dependent pathways, were investigated in prostate epitheli al cells by caspase activity assays, annexin/propidium iodide staining, cha nges in mitochondrial potential, p53, Par-4, Bax, and Bcl-2 protein levels. SMP induced p53- and Bcl-2-dependent apoptosis without activation of caspa se-3. Obviously, SMP contains protective factors that help eliminate degene rated cells and control epithelial renewal. Age-related changes in the comp osition of SMP or the susceptibility of epithelial cells might, therefore, contribute to proliferative prostatic diseases.-untergasser, G., Rumpold, H ., Plas, E., Madersbacher, S., Berger, P. A low molecular weight fraction o f human seminal plasma activates adenylyl cyclase and induces caspase 3-ind ependent apoptosis in prostatic epithelial cells by decreasing mitochondria l potential and Bcl-2/Bax ratio.