Indoxyl Sulfate Downregulates Renal Expression of Klotho through Production of ROS and Activation of Nuclear Factor-ĸB
| Autor: | Yukihiro Higashiyama, Dilinaer Bolati, Fuyuhiko Nishijima, Hidehisa Shimizu, Toshimitsu Niwa, Gulinuer Muteliefu, Atsushi Enomoto, Yusuke Higuchi, Yelixiati Adelibieke, Ayinuer Adijiang |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
Pyrrolidines Antioxidant medicine.medical_treatment Down-Regulation urologic and male genital diseases Antioxidants chemistry.chemical_compound Downregulation and upregulation Pyrrolidine dithiocarbamate Thiocarbamates Indoxyl Internal medicine medicine Animals Humans Klotho Proteins Klotho Glucuronidase chemistry.chemical_classification Regulation of gene expression Reactive oxygen species Rats Inbred Dahl business.industry NF-kappa B medicine.disease female genital diseases and pregnancy complications Acetylcysteine Rats Endocrinology Gene Expression Regulation chemistry Nephrology Reactive Oxygen Species business Indican Sesquiterpenes Kidney disease |
| Zdroj: | American Journal of Nephrology. 33:319-324 |
| ISSN: | 1421-9670 0250-8095 |
| DOI: | 10.1159/000324885 |
| Popis: | Background/Aim: Klotho, an anti-aging gene, is expressed in the kidneys, and its renal expression is decreased in chronic kidney disease (CKD). The present study aimed to examine whether renal expression of Klotho is regulated by indoxyl sulfate, a uremic toxin, using rat kidneys and human proximal tubular cells (HK-2). Methods: The effect of indoxyl sulfate on renal expression of Klotho was examined using (1) Dahl salt-resistant normotensive rats (DN), (2) Dahl salt-resistant normotensive indoxyl sulfate-administered rats (DN+IS), (3) Dahl salt-sensitive hypertensive rats (DH), and (4) Dahl salt-sensitive hypertensive indoxyl sulfate-administered rats (DH+IS). The effects of indoxyl sulfate, inhibitors of nuclear factor-ĸB (NF-ĸB) and an antioxidant on the expression of Klotho in HK-2 cells were examined. Results: DH+IS and DN+IS rats showed decreased expression of Klotho mRNA in the kidneys as compared with DH and DN rats, respectively. Indoxyl sulfate suppressed the expression of Klotho mRNA and protein in HK-2 cells, whereas an antioxidant, N-acetylcysteine, and NF-ĸB inhibitors, pyrrolidine dithiocarbamate and isohelenin, alleviated these effects. Conclusions: Indoxyl sulfate downregulates Klotho expression in kidneys through production of reactive oxygen species and activation of NF-ĸB in proximal tubular cells. Indoxyl sulfate may be involved in reduced renal expression of Klotho in CKD. |
| Databáze: | OpenAIRE |
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