INTRODUCTION: Diet and exercise affect endothelial function in the penis, but the molecular mechanisms underlying their effects are not understood. AIMS: We evaluated endothelial nitric oxide synthase (eNOS) interaction with its negative regulator caveolin-1 and eNOS uncoupling as molecular targets in the penis associated with the beneficial effects of low-fat diet and chronic exercise. METHODS: The penes were obtained from adult male Yucatan pigs fed a normal-fat or high-fat diet on exercised or sedentary regimen for 24 weeks. Markers of endothelial function (guanosine 3',5'-monophosphate [cGMP] production), endothelial dysfunction (eNOS uncoupling and eNOS interaction with caveolin-1), and oxidative stress (thiobarbituric acid reactive substances [TBARS]) were measured in the penes. The concentrations of cGMP and TBARS were determined using commercial kits. eNOS uncoupling was determined by low-temperature sodium dodecyl sulfate polyacrylamide gel electrophoresis. eNOS binding to caveolin-1, eNOS phosphorylation (Ser-1177), and protein expression of eNOS and caveolin-1 were measured by Western blot analysis in penes purified for NOS and in homogenates, respectively. MAIN OUTCOME MEASURES: Molecular parameters of endothelial function including eNOS regulatory function. RESULTS: Relative to normal-fat diet, high-fat diet significantly (P < 0.05) reduced cGMP levels and significantly (P < 0.05) increased eNOS uncoupling, eNOS binding to caveolin-1, and TBARS production in the penis of sedentary pigs. Exercise of pigs on high-fat diet reversed (P < 0.05) the abnormalities in cGMP levels, eNOS uncoupling, and eNOS binding to caveolin-1, but not TBARS levels. Exercise of pigs on normal-fat diet did not affect any of these parameters. Protein expressions of caveolin-1, phosphorylated (Ser-1177), and total eNOS were unaffected by diet or exercise. CONCLUSION: Low-fat diet and chronic exercise preserve endothelial function in the pig penis by sustaining active eNOS in its dimeric form and by limiting eNOS interaction with its negative regulator caveolin-1.
INTRODUCTION: Diet and exercise affect endothelial function in the penis, but the molecular mechanisms underlying their effects are not understood. AIMS: We evaluated endothelial nitric oxide synthase (eNOS) interaction with its negative regulator caveolin-1 and eNOS uncoupling as molecular targets in the penis associated with the beneficial effects of low-fat diet and chronic exercise. METHODS: The penes were obtained from adult male Yucatan pigs fed a normal-fat or high-fat diet on exercised or sedentary regimen for 24 weeks. Markers of endothelial function (guanosine 3',5'-monophosphate [cGMP] production), endothelial dysfunction (eNOS uncoupling and eNOS interaction with caveolin-1), and oxidative stress (thiobarbituric acid reactive substances [TBARS]) were measured in the penes. The concentrations of cGMP and TBARS were determined using commercial kits. eNOS uncoupling was determined by low-temperature sodium dodecyl sulfatepolyacrylamide gel electrophoresis. eNOS binding to caveolin-1, eNOS phosphorylation (Ser-1177), and protein expression of eNOS and caveolin-1 were measured by Western blot analysis in penes purified for NOS and in homogenates, respectively. MAIN OUTCOME MEASURES: Molecular parameters of endothelial function including eNOS regulatory function. RESULTS: Relative to normal-fat diet, high-fat diet significantly (P < 0.05) reduced cGMP levels and significantly (P < 0.05) increased eNOS uncoupling, eNOS binding to caveolin-1, and TBARS production in the penis of sedentary pigs. Exercise of pigs on high-fat diet reversed (P < 0.05) the abnormalities in cGMP levels, eNOS uncoupling, and eNOS binding to caveolin-1, but not TBARS levels. Exercise of pigs on normal-fat diet did not affect any of these parameters. Protein expressions of caveolin-1, phosphorylated (Ser-1177), and total eNOS were unaffected by diet or exercise. CONCLUSION: Low-fat diet and chronic exercise preserve endothelial function in the pig penis by sustaining active eNOS in its dimeric form and by limiting eNOS interaction with its negative regulator caveolin-1.
Authors: G García-Cardeña; P Martasek; B S Masters; P M Skidd; J Couet; S Li; M P Lisanti; W C Sessa Journal: J Biol Chem Date: 1997-10-10 Impact factor: 5.157
Authors: Biljana Musicki; Tongyun Liu; Gwen A Lagoda; Travis D Strong; Sena F Sezen; Justin M Johnson; Arthur L Burnett Journal: J Sex Med Date: 2010-09 Impact factor: 3.802
Authors: Biljana Musicki; Tongyun Liu; Travis D Strong; Gwen A Lagoda; Trinity J Bivalacqua; Arthur L Burnett Journal: J Sex Med Date: 2010-03-11 Impact factor: 3.802