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Sex difference in ischemic acute renal failure in rats: approach by proteomic analysis.

Abstract：

:It is known that female rats are resistant to ischemic acute renal failure (ARF), compared with male rats. To elucidate sex differences in ischemic ARF, we searched global protein expression in post-ischemic kidneys using proteomic techniques. Ischemic ARF was induced by 45-min ischemia followed by reperfusion. By proteomic analysis, many male- or female-dominant proteins were detected in sham-operated rat kidneys, and significantly increased or decreased proteins were found in post-ischemic kidneys 2 h after reperfusion, at which there were no significant deterioration in renal function of both sexes. We detected 86 proteins showing more than 1.5-fold significant alterations (p<0.01) in both sexes by ischemia/reperfusion (I/R) treatment. Among the altered proteins, we identified a significantly up-regulated protein in male rat kidneys, meprin alpha, a subunit of meprin which had been reported to play a role in the pathophysiology of I/R-induced ARF. In addition, it is known that a potent meprin alpha inhibitor, actinonin, can protect against I/R-induced renal injury when administered to male rats. We therefore compared the effect of actinonin on I/R-induced renal dysfunction between male and female rats. Renal function of both males and females showed significant deterioration when measured at 24 h after the reperfusion, although the degree of renal dysfunction was much less in females than in males. Pre-ischemic treatment with actinonin (30 mg/kg, i.v.) prevented the I/R-induced renal dysfunction in males but not in females. Our results provide information on differences in protein expression at an early phase after the reperfusion between male and female rats. Moreover, the present study suggests that up-regulation of meprin alpha in the post-ischemic kidney is at least partly involved in aggravation of I/R-induced renal injury in male rats. The possibility that meprin alpha is a key component of the sex difference in ischemic ARF, warrants further attention.

journal_name

Biol Pharm Bull

journal_title

Biological & pharmaceutical bulletin

authors

Takayama J,Takaoka M,Sugino Y,Yamamoto Y,Ohkita M,Matsumura Y

doi

10.1248/bpb.30.1905

subject

Has Abstract

pub_date

2007-10-01 00:00:00

pages

1905-12

issue

eissn

0918-6158

issn

1347-5215

pii

JST.JSTAGE/bpb/30.1905

journal_volume

pub_type

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Sex difference in ischemic acute renal failure in rats: approach by proteomic analysis.