Sex differences in heat shock protein 72 expression and localization in rats following renal ischemia-reperfusion injury.
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 alpha(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 alpha(1) was similar in control F and M. In postischemic F kidneys, the majority of NKA alpha(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.
Fekete
Andrea
A
Research Group for Pediatrics and Nephrology, Hungarian Academy of Sciences, Budapest, Hungary. afekete@gyer1.sote.hu
Vannay
Adám
A
Vér
Agota
A
Rusai
Krisztina
K
Müller
Veronika
V
Reusz
György
G
Tulassay
Tivadar
T
Szabó
Attila J
AJ
D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D005260:Female; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics*; D007668:Kidney / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation; D015427:Reperfusion Injury / Q000097:blood / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics
D050884:HSP72 Heat-Shock Proteins; D012333:RNA, Messenger; D003404:Creatinine