FK506 Neuroprotection After Cavernous Nerve Injury is Mediated by Thioredoxin and Glutathione Redox Systems

Gwen Lagoda, Yi Xie, Sena F. Sezen, K. Joseph Hurt, Limin Liu, Biljana Musicki, Arthur Burnett

Research output: Contribution to journalArticle

Abstract

Introduction. Immunophilin ligands such as FK506 (FK) preserve erectile function (EF) following cavernous nerve injury (CNI), although the precise mechanisms are unclear. We examined whether the thioredoxin (Trx) and glutathione (GSH) redox systems mediate this effect after CNI. Aim. To investigate the roles of Trx reductase 2 (TrxR2) and S-Nitrosoglutathione reductase (GSNOR) as antioxidative/nitrosative and antiapoptotic mediators of the neuroprotective effect of FK in the penis after CNI. Methods. Adult male rats, wild-type (WT) mice, and GSNOR deficient (GSNOR -/-) mice were divided into four groups: sham surgery (CN [cavernous nerves] exposure only)+vehicle; sham surgery+FK (5mg/kg/day/rat or 2mg/kg/day/mouse, for 2days, subcutaneous); CNI+vehicle; and CNI+FK. At day 4 after injury, electrically stimulated changes in intracavernosal pressure (ICP) were measured. Penises were collected for Western blot analysis of TrxR2, GSNOR, and Bcl-2, and for immunolocalization of TrxR2 and GSNOR. Main Outcome Measures. EF assessment represented by maximal ICP and total ICP in response to electrical stimulation. Evaluation of protein expression levels and distribution patterns of antioxidative/nitrosative and antiapoptotic factors in penile tissue. Results. EF decreased after CNI compared with sham surgery values in both rats (P

Original languageEnglish (US)
Pages (from-to)3325-3334
Number of pages10
JournalJournal of Sexual Medicine
Volume8
Issue number12
DOIs
StatePublished - Dec 2011

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Thioredoxins
Tacrolimus
Oxidation-Reduction
Glutathione
Wounds and Injuries
Mouse Adh5 protein
Penis
glutathione-independent formaldehyde dehydrogenase
Pressure
Thioredoxin Reductase 2
Oxidoreductases
Immunophilins
Neuroprotective Agents
Neuroprotection
Electric Stimulation
Western Blotting
Outcome Assessment (Health Care)
Ligands

Keywords

  • Apoptosis
  • Erectile dysfunction
  • Neuroprotective effect
  • Nitrosylation
  • Oxidative stress
  • Penis

ASJC Scopus subject areas

  • Urology
  • Obstetrics and Gynecology
  • Reproductive Medicine

Cite this

FK506 Neuroprotection After Cavernous Nerve Injury is Mediated by Thioredoxin and Glutathione Redox Systems. / Lagoda, Gwen; Xie, Yi; Sezen, Sena F.; Hurt, K. Joseph; Liu, Limin; Musicki, Biljana; Burnett, Arthur.

In: Journal of Sexual Medicine, Vol. 8, No. 12, 12.2011, p. 3325-3334.

Research output: Contribution to journalArticle

Lagoda, Gwen ; Xie, Yi ; Sezen, Sena F. ; Hurt, K. Joseph ; Liu, Limin ; Musicki, Biljana ; Burnett, Arthur. / FK506 Neuroprotection After Cavernous Nerve Injury is Mediated by Thioredoxin and Glutathione Redox Systems. In: Journal of Sexual Medicine. 2011 ; Vol. 8, No. 12. pp. 3325-3334.
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