Abstract: TH-PO301

Gender Differences in Renal Ischemia/Reperfusion Injury and the Protective Role of Sigma-1 Receptor

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic

Authors

  • Hosszu, Adam, Semmelweis University, Budapest, Hungary
  • Antal, Zsuzsanna, Semmelweis University, Budapest, Hungary
  • Lenart, Lilla, Semmelweis University, Budapest, Hungary
  • Szkibinszkij, Edgar, Semmelweis University, Budapest, Hungary
  • Balogh, Dora Bianka, Semmelweis University, Budapest, Hungary
  • Vannay, Ádám, MTA-SE Pediatrics and Nephrology Research Group, Budapest, Hungary
  • Szabo, Attila J., Semmelweis University, Budapest, Hungary
  • Wagner, Laszlo J., Semmelweis University, Budapest, Hungary
  • Fekete, Andrea, MTA-SE "Lendulet" Diabetes Research Group, Budapest, Hungary
Background

Gender differences in the susceptibility to renal ischemia/reperfusion injury (IRI) is a known phenomenon. Tubular dysfunction following IRI can be prevented by heat shock proteins. We recently showed that Sigma-1 receptor (S1R) activation is protective in IRI through inducing the Akt-nitric oxide synthase molecular pathway. 17β-estradiol is known to have estrogen receptor-independent effects, possibly through modulating S1R which could explain superior outcomes in females.
We aimed to describe gender differences in S1R expression and the heat shock response; to prove that S1R activation by 17β-estradiol or dehidroepiandrosterone (DHEA) induces the heat shock response and is thus involved in gender differences in renal IRI.

Methods

Adult female (F), male (M), ovariectomized female (Ovx), and S1R agonist DHEA-treated male (DHEA) Wistar rats (n=8/group) were subjected to 50 min renal ischemia. Kidneys were harvested 2 hours (T2) or 24 hours (T24) after reperfusion. Renal function and structural damage were assessed. Renal protein levels of S1R, phospho-Akt (Ser473), HSF-1, HSP72, HSP27 and Na+/K+-ATP-ase (NKA) were determined. Protein localization was determined by fluorescent immunohistochemistry.

Results

Renal function of F and DHEA rats was less impaired compared to M and Ovx. Structural lesions were less prominent in F, Ovx and DHEA rats than in M. S1R protein increased only in F and DHEA at T2, but returned to baseline by T24. Akt phosphorylation was induced in F and after DHEA treatment at T2. Heat shock response proteins (HSF-1, HSP72 and HSP27) were induced after IRI and were markedly more increased in F and DHEA rats than M and Ovx. Baseline NKA protein levels were higher in F rats. NKA disruption after IRI was suppressed in F and DHEA rats. In M and Ovx females NKA translocated from the basal membrane of tubular cells, thereby losing its function, while in F and DHEA rats it was mainly preserved in its physiological location colocalized with HSP72.

Conclusion

We confirmed previous data indicating that females are less prone to IRI than males. We showed that ovariectomy diminishes the protection that female rats enjoy. We identified S1R activation by 17β-estradiol or DHEA as a possible mediator of protective mechanisms in renal IRI by inducing the heat shock response.