Sex Difference in Ischemic Acute Renal Failure in Rats : Approach by Proteomic Analysis(Pharmacology)
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概要
- 論文の詳細を見る
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.
- 公益社団法人日本薬学会の論文
- 2007-10-01
著者
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OHKITA Mamoru
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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MATSUMURA Yasuo
Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences
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Takaoka Masanori
Department Of Internal Medicine Iii Osaka Medical College
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Teragaki M
Department Of Internal Medicine And Cardiology Osaka City University Graduate School Of Medicine
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Ohkita Mamoru
Laboratory Of Pathological And Molecular Pharmacology Osaka University Of Pharmaceutical Sciences
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YAMAMOTO Yuji
Laboratory of Nutritional Biochemistry, Department of Applied Biology and Chemistry, Faculty of Appl
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Muro Takashi
Department Of Internal Medicine And Cardiology Osaka City University Medical School
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Matsumura Yasuo
Laboratory Of Pathological And Molecular Pharmacology Osaka University Of Pharmaceutical Sciences
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Matsumura Yasuo
Department Of Pharmacology Osaka University Of Phiarmaceutical Sciences
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Matsumura Y
Asahi Glass Co. Ltd. Tokyo Jpn
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Okabe Makoto
Third Division Department Of Internal Medicine Osaka Medical College
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Mori Tatsuhiko
Third Department Of Medicine Osaka Medical College
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Takaoka M
Laboratory Of Pathological And Molecular Pharmacology Osaka University Of Pharmaceutical Sciences
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Takayama Junji
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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Okabe Makoto
The Third Division Internal Medicine Osaka College
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Takeuchi Masaaki
Second Department Of Internal Medicine University Of Occupational And Environmental Health School Of
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Shiota Y
Laboratory Of Pathological And Molecular Pharmacology Osaka University Of Pharmaceutical Sciences
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Yamamoto Yuji
Laboratory Of Cellular Microbiology School Of Veterinary Medicine Kitasato University
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Mori Tatsuhiko
Department Of Gastroenterology And Neurology Faculty Of Medicine Kagawa University
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Takaoka Masanori
Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, Japan
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