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Iron chelation and a free radical scavenger suppress angiotensin II‐induced downregulation of klotho , an anti‐aging gene, in rat
Author(s) -
Saito Kan,
Ishizaka Nobukazu,
Mitani Haruo,
Ohno Minoru,
Nagai Ryozo
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)00894-9
Subject(s) - klotho , downregulation and upregulation , angiotensin ii , chemistry , endocrinology , renin–angiotensin system , medicine , oxidative stress , free radical scavenger , gene expression , kidney , biology , biochemistry , gene , receptor , blood pressure
Administration of angiotensin II 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 2α (8‐epi‐PGF 2α ), 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.