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Sex differences in heat shock protein 72 expression and localization in rats following renal ischemia-reperfusion injury

¹Research Group for Pediatrics and Nephrology, Hungarian Academy of Sciences, ²1st Department of Pediatrics, ⁴Institute of Medical Chemistry, Molecular Biology, and Pathobiochemistry, and ⁵Department of Pulmonology, Semmelweis University, and ³Szentágothai Knowledge Center, Budapest, Hungary

Submitted 8 March 2006 ; accepted in final form 10 April 2006

Previously, we demonstrated gender differences in Na-K-ATPase (NKA) expression and function after renal ischemia-reperfusion (I/R) injury (Sex differences in the alterations of Na⁺, K⁺-ATPase following ischemia-reperfusion injury in the rat kidney. J Physiol 555: 471–480, 2004). Postischemic membrane destruction causes inhibition of NKA, whereas heat shock protein (HSP) 72 helps to preserve it. We tested the sex differences in postischemic expression of HSP72 and colocalization with NKA. The left renal pedicle of uninephrectomized female (F) and male (M) Wistar rats was clamped for 55 min followed by 2 (T2), 16 (T16), and 24 h (T24) of reperfusion. Uninephrectomized, sham-operated F and M rats served as controls. Postischemic blood urea nitrogen (BUN), serum creatinine, and renal histology were analyzed. HSP72 mRNA expression was detected by RT-PCR, protein levels by Western blot analysis. Fluorescent immunohistochemistry was performed to evaluate the localization of HSP72 and NKA ₁-subunit. Postischemic BUN and creatinine were higher, and renal histology showed more rapid progression in M vs. F (P < 0.05). HSP72 mRNA expression was higher in F vs. M in control and in all I/R groups (P < 0.05). Similar changes were observed in HSP72 protein levels (F vs. M, P < 0.05, control, T2, T16, T24, respectively). Immunohistochemical localization of HSP72 and NKA ₁ was similar in control F and M. In postischemic F kidneys, the majority of NKA ₁ and HSP72 was colocalized on the basolateral membrane of tubular cells, whereas in M prominent staining was observed in the cytosol and apical domain. This study indicates that in female kidneys the higher basal and postischemic levels of HSP72 and different colocalization with NKA might contribute to the gender differences in renal I/R injury.

gender

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