Sex Difference in Ischemic Acute Renal Failure in Rats: Approach by Proteomic Analysis
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- Takayama Junji
- Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences
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- Takaoka Masanori
- Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences
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- Sugino Yohko
- Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences
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- Yamamoto Yuji
- Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences
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- Ohkita Mamoru
- Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences
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- Matsumura Yasuo
- Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences
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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 α, 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 α 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 α 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 α is a key component of the sex difference in ischemic ARF, warrants further attention.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 30 (10), 1905-1912, 2007
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679601786624
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- NII論文ID
- 110006436373
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- NII書誌ID
- AA10885497
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- COI
- 1:CAS:528:DC%2BD2sXhtl2jtLfN
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 8919241
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- PubMed
- 17917260
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可