Periprostatic adipose tissue (PPAT) supernatant from obese mice releases anticontractile substances and increases human prostate epithelial cell proliferation: the role of nitric oxide and adenosine

Background: The prostate gland is surrounded by periprostatic adipose tissue (PPAT) that can release mediators interfere in function. In this study, we examined the effect of supernatant obtained from obese mice on reactivity vitro and viability human prostatic epithelial cell lines. Methods: Male C57BL/6 were fed a standard or high-fat diet after which PPAT was isolated, incubated Krebs-Henseleit solution for 30 min (without prostate) 60 (with prostate), then collected screened biological activity. Total nitrate nitrite (NOx − ) adenosine quantified, NOx quantified. Concentration-response curves to phenylephrine (PE) lean with without tissue. some experiments, co-incubated inhibitors nitric oxide (NO)-cyclic guanosine monophosphate pathway (L-NAME, 1400W, ODQ), adenylate cyclase (SQ22536) A 2A (ZM241385), 2B (MRS1754) receptor antagonists. PNT1-A (normal) BPH-1 (hyperplasic) cells cultured 24, 48, 72 h absence presence these inhibitors/antagonists, proliferation assessed. Results: levels significantly higher (30 min, when compared vehicle. trend toward an increase NOX observed min. reduced PE-induced contractions only mice. co-incubation L-NAME, ODQ, ZM241385 attenuated anticontractile activity supernatant. Incubation increased expression apoptosis marker protein caspase-3 Hyperplastic (BPH-1) showed greater 24 h, 48 culture medium alone. NO-signaling antagonists h. Conclusion: NO are involved pro-proliferative activities More studies needed determine whether blockade and/or derived improve