• Home
  • Search Results
  • Hydroxyl fasudil, an inhibitor of Rho signaling, improves erectile function in diabetic rats: a role for neuronal ROCK.

Hydroxyl fasudil, an inhibitor of Rho signaling, improves erectile function in diabetic rats: a role for neuronal ROCK.

The journal of sexual medicine (2014-06-13)
Sena F Sezen, Gwen Lagoda, Biljana Musicki, Arthur L Burnett
ABSTRACT

The pathogenesis of diabetic erectile dysfunction (ED) includes neuropathy, but the molecular basis for neurogenic ED is incompletely understood. The RhoA/ROCK pathway has been implicated in diabetic neuropathy and in ED, but its role in diabetic neurogenic ED is not known. The aim of this study was to determine whether hydroxyl fasudil, a ROCK inhibitor, affects diabetic neuropathy-related ED. Type 1 diabetes mellitus was induced in male rats by streptozotocin (75 mg/kg, intraperitoneally). After 8 weeks, diabetic rats were administered hydroxyl fasudil, a selective ROCK inhibitor (10 mg/kg/day, intraperitoneally) or vehicle, for 4 weeks. Age-matched control, nondiabetic, rats were treated intraperitoneally for 4 weeks with saline. At week 12, after a 2 day washout, neuro-stimulated erectile function was evaluated. Major pelvic ganglia (MPG) were collected for Western blot analysis of RhoA, ROCK-1, ROCK-2, phospho (P)-AKT (Ser(473) ), and P-phosphatase and tensin homolog (P-PTEN) (Ser(380) /Thr(382/383) ). Effect of ROCK inhibitor hydroxyl fasudil on erectile function and ROCK/P-AKT/P-PTEN pathway in the MPG of diabetic rats. Erectile response was significantly (P < 0.05) reduced in diabetic rats compared with nondiabetic rats and was preserved (P < 0.05) in diabetic rats treated with hydroxyl fasudil. In diabetic rats, RhoA and ROCK-2 protein expressions in MPG were increased (P < 0.05) and remained increased in hydroxyl fasudil-treated rats. P-AKT (Ser(473) ) expression was decreased (P < 0.05), whereas P-PTEN (Ser(380) /Thr(382/383) ) expression was increased (P < 0.05) in MPG of diabetic rats compared with nondiabetic rats, and both were reversed (P < 0.05) in diabetic rats treated with hydroxyl fasudil. Improved erectile function and restored P-AKT and P-PTEN in the MPG with hydroxyl fasudil treatment suggest the role of Rho signaling via PTEN/AKT pathway in neurogenic diabetic ED.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-AKT antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-AKT antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-AKT1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-phospho-PTEN (pSer385) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-AKT1 antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-AKT antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-AKT antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-Akt1 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-AKT1 (Ab-473) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-AKT1 (Ab-450) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-AKT1 (Ab-308) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-phospho-PTEN (pSer380/pThr382/pThr383) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Monoclonal Anti-AKT1 antibody produced in mouse, clone 6D6, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-AKT1 antibody produced in mouse, clone 2H1, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-AKT1 antibody produced in mouse, clone 4B9, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-AKT1 antibody produced in mouse, clone 6G6, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Anti-AKT1 antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-AKT1 (ab1) antibody produced in chicken, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-AKT1 antibody produced in mouse, clone 2E11, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-Rac antibody produced in mouse, clone 23A8, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Rabbit anti-AKT1 Antibody, Affinity Purified, Powered by Bethyl Laboratories, Inc.