Sex differences in the alterations of Na+,K+-ATPase following ischaemiaâreperfusion injury in the rat kidney
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 ischaemiaâreperfusion (I-R)...
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| Published in: | The Journal of physiology Vol. 555; no. 2; p. 471 |
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| Main Authors: | , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
The Physiological Society
01-03-2004
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| Online Access: | Get full text |
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| Summary: | 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 ischaemiaâreperfusion (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 â 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. |
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| ISSN: | 0022-3751 1469-7793 |
| DOI: | 10.1113/jphysiol.2003.054825 |