FK506 and Rapamycin Neuroprotect Erection and Involve Different Immunophilins in a Rat Model of Cavernous Nerve Injury |
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| Authors: | Gwen Lagoda Sena F. Sezen Arthur L. Burnett |
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| Affiliation: | 1. The James Buchanan Brady Urological Institute, The Johns Hopkins Hospital and The Johns Hopkins University School of Medicine—Department of Urology, Baltimore, MD, USA;1. Department of Medicine, Universita'' di Verona, Verona, Italy;2. Department of Biomedical Sciences and Human Oncology, Section of Clinical Oncology, University of Bari ''A. Moro'', Bari, Italy;3. Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy;4. Division Oncology, Regina Elena Institute, Rome, Italy;5. UO Multidisciplinare di Patologia Mammaria, US Terapia Molecolare e Farmacogenomica, AZ. Istituti Ospitalieri di Cremona, Cremona, Italy;6. Supportive Care in Cancer Unit, Department of Hematology and Pediatric Onco-Hematology, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy;7. Division of Medical Senology, European Institute of Oncology, Milan, Italy;8. Oncologia Medica 2, Istituto Oncologico Veneto IRCCS, Padova, Italy;9. UO Sviluppo Terapie Innovative, IRCCS AOU San Martino, IST, National Institute for Cancer Research, Genoa, Italy;10. Department of Endocrinology and Molecular and Clinical Oncology, University of Naples Federico II, Naples, Italy;11. Oncology Unit, IRCC Candiolo, Torino, Italy;12. Department of Medical Oncology, University Campus Bio-Medico, Rome, Italy;1. Department of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany;2. Center for Primary Health Care Research, Lund University, Malmö, Sweden;3. Department of Genetics, Cancer Research Institute of Slovak Academy of Sciences, Vlarska 7, 83391 Bratislava, Slovakia;4. Faculty of Medicine, Slovak Medical University, Limbova 12, 83303 Bratislava, Slovakia;5. Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 14200 Prague, Czech Republic;6. Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Albertov 4, 12800 Prague, Czech Republic;7. Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, 30605 Pilsen, Czech Republic;8. Human Genetics Foundation, Turin, Italy;9. Department of Public Health, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Sklabinska 26, 03601 Martin, Slovakia;10. Health Effects Laboratory, Department of Environmental Chemistry, NILU-Norwegian Institute for Air Research, Instituttveien 18, 2007 Kjeller, Norway;11. Clinic of Occupational Medicine and Toxicology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava and University Hospital Martin, Kollarova 2, 03601 Martin, Slovakia |
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| Abstract: | IntroductionImmunophilin ligands function by binding to receptor proteins such as FK506 binding proteins (FKBPs). FKBPs are studied for their roles in neuroprotection.AimCompare the effect of FK506 (FK) and rapamycin (RAP) on erectile function (EF) recovery and FKBP expressions in penis and major pelvic ganglion (MPG) after cavernous nerve (CN) injury.MethodsAdult male rats were divided into four groups: sham surgery (CN exposure only) + vehicle; bilateral CN injury (BCNI; bilateral crush, 3 minutes with hemostat clamp) + vehicle; BCNI + FK (5 mg/kg/day, 5 days, sc); and BCNI + RAP (2 mg/kg/day, 5 days, sc). At both 24 hours (Day 1) or 1 week (Day 7) after BCNI, EF was assessed by intracavernosal pressure measurement and FKBPs 12, 38, 52, and 65 expressions were evaluated by Western blot analysis in collected penises and MPGs.Main Outcome MeasuresEF and change in protein expressions of FKBPs in the rat penis and MPG after BCNI with and without immunophilin ligand treatment.ResultsBoth FK- and RAP-treated rats had preserved EF compared with vehicle-treated rats after BCNI. FKBPs changed variably following injury and treatment. In particular, in the penis at Day 1, FKBP 38 expression was decreased after BCNI and both FK and RAP attenuated this decrease. In MPG at Day 1, FKBP 38 expression was also decreased after BCNI and FK attenuated the decrease, while at Day 7, FKBP 38 expression was still decreased and RAP attenuated the decrease. Also, in the penis at Day 1, FKBP 65 expression decreased after BCNI and FK attenuated the decrease. In the MPG, FKBP 65 expression increased at both Days 1 and 7 with FK treatment.ConclusionsImproved EF after BCNI, as shown with RAP, further suggests a role of immunophilin ligands as a protective therapy of CN injury associated erectile dysfunction. Our findings also suggest that select FKBPs, such as FKBP 38 and FKBP 65, may mediate these effects. Lagoda G, Sezen SF, and Burnett AL. FK506 and rapamycin neuroprotect erection and involve different immunophilins in a rat model of cavernous nerve injury. J Sex Med 2009;6:1914–1923. |
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