Functional significance of hsp90‐eNOS interaction in penile tissues
Makaleler > Tam Makale · 2013
Yazarlar: Günay YETİK ANACAK, Elif ERTUNA, Gönen ÖZŞARLAK SÖZER, Saadet Turkseven di Pascoli, Ersin Oğuz KOYLU, Oguz Gozen, Gülnur SEVİN, Mehmet Zuhuri ARUN, Ismail Un
The FASEB Journal, Uluslararası, Wos, 2013, cilt 27
DOI: 10.1096/fasebj.27.1_supplement.920.5
Özet
Heat shock protein 90 (hsp90) regulates the NO‐cGMP pathway in several vascular tissues. In the present study, we investigated the existence and functional significance of hsp90‐eNOS interactions in murine penile tissues. Utilizing double‐labeled anti‐eNOS and anti‐hsp90 antibodies we observed co‐localization of hsp90 and eNOS by immunofluorescence in mouse corpus cavernosum (MCC). Additionally, hsp90‐eNOS interaction was demonstrated in co‐immunoprecipitation studies. To study the functional significance of these interactions, we examined the sensitivity of eNOS‐dependent relaxation of MCC to hsp90 inhibitors, radicicol and 17‐AAG. Pretreatment with radicicol (10 μg/ml) or 17AAG (400 nM) for 15 hours disrupted the hsp90‐eNOS complex (as demonstrated by co‐immunoprecitation experiments) and significantly reduced the acetylcholine‐, bradykinin‐ and sphingosine‐induced eNOS‐dependent relaxation of pre‐contracted MCC. Furthermore, 17‐AAG decreased MCC constriction induced by the eNOS inhibitor, LNA. Endothelium‐independent relaxations induced by papaverine or NTG were not affected by hsp90 inhibition, suggesting the absence of sGC regulation by hsp90 in MCC. We conclude that hsp90 forms complexes with eNOS and that it regulates both basal and agonist‐evoked eNOS activation in MCC. (Supported by TUBA GEBIP‐2010, TUBITAK 109S453, EBILTEM 2011/BIL/002 and FABAL).