2015 Fiscal Year Final Research Report
Selective estrogen receptor modulator attenuates albumin-induced apoptosis in renal proximal tubules through inhibition of mitochondrial stress
| Project/Area Number |
25461238
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KASHIHARA Naoki 川崎医科大学, 医学部, 教授 (10233701)
SATOH Minoru 川崎医科大学, 医学部, 准教授 (70449891)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | 尿細管間質障害 / エストロゲン / ラロキシフェン / 蛋白尿 / ミトコンドリア / 酸化ストレス |
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| Outline of Final Research Achievements |
Ｗe investigated whether the selective estrogen receptor modulator, raloxifene, could attenuate albumin-induced tubular injury through reducing mitochondrial oxidative stress.ICR-derived glomerulonephritis (ICGN) mice, a mouse strain with a hereditary nephrotic syndrome, underwent ovariectomy, and were treated with raloxifene (50μg/kg/day) for 6 weeks. Ovariectomy induced the apoptotic cell death in renal proximal cells (terminal deoxynucleotidyl transferase dUTP nick-end labeling staining) and decreased cytochrome-c oxidase activity in mitochondria. Electron microscopy of the ovariectomized ICGN mice revealed morphologically abnormal mitochondria, and these changes were suppressed following treatment with raloxifene with upregulation of the mitochondrial thioredoxin system. Stimulation of estrogen receptor attenuated programmed cell death in renal proximal tubules induced by albumin-overload as a result of amelioration of mitochondrial dysfunction.
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| Free Research Field |
腎臓内科
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