Iron chelation and a free radical scavenger suppress angiotensin II-induced downregulation of klotho, an anti-aging gene, in rat

被引：70

作者：

Saito, K ^{[1
]}

Ishizaka, N ^{[1
]}

Mitani, H ^{[1
]}

Ohno, M ^{[1
]}

Nagai, R ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Cardiovasc Med, Bunkyo Ku, Tokyo 1138655, Japan

来源：

FEBS LETTERS | 2003年 / 551卷 / 1-3期

关键词：

angiotensin II; aging; iron metabolism; kidney; oxidative stress;

D O I：

10.1016/S0014-5793(03)00894-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Administration of angiotensin H to rats decreases renal expression of klotho, an aging-related gene, and also causes abnormal iron deposition in renal cells. Here we have examined the effects of iron overload and iron chelation on renal expression of klotho in untreated rats and rats treated with angiotensin II. Administration of iron-dextran caused a downregulation of klotho expression, and iron chelation suppressed the angiotensin II-induced downregulation of this gene. In addition, a free radical scavenger (T-0970), which effectively decreased plasma levels of 8-epi-prostaglandin F-2alpha (8-epi-GF(2alpha)), suppressed angiotensin II-induced downregulation of klotho. Collectively, these findings suggest that abnormal iron metabolism and increased oxidative stress are involved in the mechanism of angiotensin II-mediated modulation of klotho expression. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：58 / 62

页数：5

共 17 条

[11] Endothelial dysfunction in the klotho mouse and downregulation of klotho gene expression in various animal models of vascular and metabolic diseases [J].

Nagai, R ;

Saito, Y ;

Ohyama, Y ;

Aizawa, H ;

Suga, T ;

Nakamura, T ;

Kurabayashi, M ;

Kuro-o, M .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2000, 57 (05) :738-746

[12] Cognition impairment in the genetic model of aging klotho gene mutant mice:: a role of oxidative stress [J].

Nagai, T ;

Yamada, K ;

Kim, HC ;

Kim, YS ;

Noda, Y ;

Imura, A ;

Nabeshima, Y ;

Nabeshima, T .

FASEB JOURNAL, 2002, 16 (13) :50-+

[13]

OHASHI N, 2000, IN PRESS J CHROMATOG

[14] Therapeutic effect of a newly developed antioxidative agent (OPC-15161) on experimental immune complex nephritis [J].

Sanaka, T ;

Nakano, Y ;

Nishimura, H ;

Shinobe, M ;

Higuchi, C ;

Omata, M ;

Nihei, H ;

Sugino, N .

NEPHRON, 1997, 76 (03) :315-322

[15] Disruption of the klotho gene causes pulmonary emphysema in mice -: Defect in maintenance of pulmonary integrity during postnatal life [J].

Suga, T ;

Kurabayashi, M ;

Sando, Y ;

Ohyama, Y ;

Maeno, T ;

Maeno, Y ;

Aizawa, H ;

Matsumura, Y ;

Kuwaki, T ;

Kuro-o, M ;

Nabeshima, Y ;

Nagai, R .

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2000, 22 (01) :26-33

[16] Antioxidative property of T-0970, a new ureidophenol derivative [J].

Suzumura, K ;

Hashimura, Y ;

Kubota, H ;

Ohmizu, H ;

Suzuki, T .

FREE RADICAL RESEARCH, 2000, 32 (03) :255-264

[17] Troglitazone improves endothelial function and augments renal klotho mRNA expression in Otsuka Long-Evans Tokushima Fatty (OLETF) rats with multiple atherogenic risk factors [J].

Yamagishi, T ;

Saito, Y ;

Nakamura, T ;

Takeda, S ;

Kanai, H ;

Sumino, H ;

Kuro-O, M ;

Nabeshima, Y ;

Kurabayashi, M ;

Nagai, R .

HYPERTENSION RESEARCH, 2001, 24 (06) :705-709

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