A low-molecular-weight fraction of human seminal plasma activates adenylyl cyclase 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 the prostate that are governed by endocrine factors and local stromal/epithelial and luminal/epithelial interactions. Prostate epithelial cells secrete numerous factors into the seminal plasma (SMP) that are thought to be responsible for nutrition, accurate pH, and ionic environment of sperm. Our hypothesis assumes that prostatic factors responsible for optimal fertility might have retrograde influences on epithelial cell growth, differentiation, and function. SMP was analyzed for proteins and other biologically active substances by size exclusion high-performance liquid chromatography. Each fraction was investigated for its effect on cell growth and death. A low molecular mass fraction (2-4 kDa) was responsible for inducing apoptosis in proliferating prostate epithelial cells. Signal transduction was mediated by the 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 epithelial cells by caspase activity assays, annexin/propidium iodide staining, changes in mitochondrial potential, p53, Par-4, Bax, and Bcl-2 protein levels. SMP induced p53- and Bcl-2-dependent apoptosis without activation of caspase-3. Obviously, SMP contains protective factors that help eliminate degenerated cells and control epithelial renewal. Age-related changes in the composition of SMP or the susceptibility of epithelial cells might, therefore, contribute to proliferative prostatic diseases
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria.
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G
Untergasser
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H
Rumpold
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E
Plas
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S
Madersbacher
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P
Berger
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000328:Adult; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival; D002851:Chromatography, High Pressure Liquid; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009940:Organoids / Q000166:cytology; D011467:Prostate / Q000166:cytology* / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012661:Semen / Q000737:chemistry*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D000262:Adenylyl Cyclases