Involvement of RhoA/Rho-kinase in L-cysteine/H2S pathway-induced inhibition of agonist-mediated corpus cavernosal smooth muscle contraction

Aydinoglu F., ADıBELLI E., Yılmaz-Oral D., Ogulener N.

NITRIC OXIDE-BIOLOGY AND CHEMISTRY, cilt.85, ss.54-60, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 85
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1016/j.niox.2019.02.001
  • Dergi Adı: NITRIC OXIDE-BIOLOGY AND CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.54-60
  • Anahtar Kelimeler: L-cysteine/H2S pathway, RhoA/Rho-kinase, MYPT1 activity, H2S level, Mouse corpus cavernosum, SULFIDE-INDUCED RELAXATION, HYDROGEN-SULFIDE, NITRIC-OXIDE, RHO-KINASE, H2S, ARTERIES, MECHANISM, PROTEINS
  • Çukurova Üniversitesi Adresli: Evet

Özet

Rho-kinase activity is a key regulator in the maintenance of corporal vasoconstriction and penile detumescense. Also, importance of L-cysteine/H2S pathway in erectile tissue has been shown; however it is currently unknown the role RhoA/Rho-kinase pathway in H2S-induced inhibition in cavernosal tissue. We investigated the role of RhoA/Rho-kinase pathway in the inhibitory effect of L-cysteine and NaHS, as endogenous and exogenous H2S, respectively, on phenylephrine-induced contractions of mouse cavernosal strips. Phenylephrine, alpha(1) receptor agonist, (10 nM-100 mu M) induced a concentration-dependent contraction in CC. L-cysteine (endogenous H2S substrate; 10 mM) and exogenous H2S (NaHS; 1 mM) significantly inhibited the contractile response to phenylephrine (P < 0.05). Inhibition of CSE and CBS enzymes by PAG (10 mM) and AOAA (1 mM), respectively, significantly reversed the inhibitory effects of L-cysteine on phenylephrine-induced contraction (P < 0.05). Y-27632 (1 mu M), a specific Rho-kinase inhibitor, significantly augmented the inhibitory effect of L-cysteine and NaHS on phenylephrine-induced contraction, and this inhibition was reversed by PAG and AOAA (P < 0.05). In addition, the formation of H2S was increased by approximately 1.8 fold over basal values after incubation of tissue homogenates with L-cysteine. Y-27632 significantly increased both basal and L-cysteine-induced H2S formation and this augmentation diminished by PAG and AOAA (P < 0.05). Furthermore, the pMYPT-1 expression was significantly decreased by L-cysteine, NaHS or Y-27632 alone. Also, pMYPT-1 expression was completely abolished by the L-cysteine/NaHS plus Y-27632 combination, and this inhibition was reversed by PAG and AOAA (P < 0.05). These results suggest that there is an interaction between Rho-kinase and H2S pathways. Rho-kinase may be, at least in part, inhibits CSE/CBS enzymes in mouse corpus cavernosal tissue; however, it is not excluded the other kinases such as PKC and Zip-kinase.