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Sex differences in the alterations of Na + ,K + ‐ATPase following ischaemia–reperfusion injury in the rat kidney
Author(s) -
Fekete Andrea,
Vannay Ádám,
Vér Ágota,
Vásárhelyi Barna,
Müller Veronika,
Ouyang Nengtai,
Reusz György,
Tulassay Tivadar,
Szabó Attila J.
Publication year - 2004
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2003.054825
Subject(s) - creatinine , blood urea nitrogen , kidney , medicine , endocrinology , pathogenesis , western blot , ischemia , chemistry , histology , biochemistry , gene
Postischaemic acute renal failure (ARF) is influenced by sex. Na + ,K + ‐ATPase (NKA) plays a crucial role in the pathogenesis of postischaemic ARF. We tested the impact of sex on mRNA, protein expression, cellular distribution and enzyme activity of NKA following renal ischaemia–reperfusion (I‐R) injury. The left renal pedicle of uninephrectomized female (F) and male (M) Wistar rats was clamped for 55 min followed by 2 h (T2) and 16 h (T16) of reperfusion. Uninephrectomized, sham‐operated F and M rats served as controls ( n = 6 per group). Blood urea nitrogen, serum creatinine and renal histology were evaluated to detect the severity of postischaemic ARF. mRNA expression of NKA α1 and β1 subunits were detected by RT‐PCR. The effect of I‐R on cellular distribution was compared by Triton X‐100 extraction. Cellular proteins were divided into Triton‐insoluble and Triton‐soluble fractions and assessed by Western blot. NKA enzyme activity was also determined. After the ischaemic insult blood urea nitrogen and serum creatinine were higher and renal histology showed more rapid progression in M versus F ( P < 0.05). mRNA expression of the NKA α1 subunit decreased in I‐R groups versus controls, but was higher in F versus M both in control and I‐R groups ( P < 0.05). However, protein levels of the NKA α1 subunit in total tissue homogenate did not differ in controls, but were higher in F versus M in I‐R groups ( P < 0.05). Triton X‐100 extractability was lower in F versus M at T16 ( P < 0.05). NKA enzyme activity was the same in controls, but was higher in F versus M in I‐R groups (T2: 14.9 ± 2.3 versus 9.15 ± 2.21 U) (T16: 11.7 ± 4.1 versus 5.65 ± 2.3 U; P < 0.05). mRNA and protein expression of the NKA β1 subunit did not differ between F and M in any of the protocol. We concluded that NKA is more protected from the detrimental effects of postischaemic injury in females. Higher mRNA and protein expression of the NKA α1 subunit and higher enzyme activity might be additional contributing factors to the improved postischaemic renal function of female rats.