| Cyclosporine A induces senescence in renal tubular epithelial cells. | |
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MedLine Citation:
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PMID: 17596534 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The nephrotoxic potential of the widely used immunosuppressive agent cyclosporine A (CsA) is well recognized. However, the mechanism of renal tubular toxicity is not yet fully elucidated. Chronic CsA nephropathy and renal organ aging share some clinical features, such as renal fibrosis and tubular atrophy, raising the possibility that CsA may exert some of its deleterious effects via induction of a stress-induced senescent phenotype. We investigated this hypothesis in HK-2 cells and primary proximal tubular cells in vitro. CsA induced the production of H2O2, caused cell cycle arrest in the G0/G1 phase, and inhibited DNA synthesis. Furthermore, CsA exposure lead to a reduction of telomere length, increased p53 serine 15 phosphorylation, and caused an upregulation of the cell cycle inhibitor p21(Kip1) (CDKN1A) mRNA levels. CsA caused an increase in p16(INK4a) (CDKN2A) expression after a 13-day exposure in primary proximal tubular cells but not in HK-2 cells. Coincubation of cells with CsA and catalase was able to prevent telomere shortening and partially restored DNA synthesis. In summary, CsA induces cellular senescence in human renal tubular epithelial cells, which can be attenuated by scavenging reactive oxygen species. |
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Authors:
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Paul Jennings; Christian Koppelstaetter; Sonia Aydin; Thomas Abberger; Anna Maria Wolf; Gert Mayer; Walter Pfaller |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-06-27 |
Journal Detail:
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Title: American journal of physiology. Renal physiology Volume: 293 ISSN: 1931-857X ISO Abbreviation: Am. J. Physiol. Renal Physiol. Publication Date: 2007 Sep |
Date Detail:
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Created Date: 2007-08-31 Completed Date: 2007-10-29 Revised Date: 2011-04-28 |
Medline Journal Info:
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Nlm Unique ID: 100901990 Medline TA: Am J Physiol Renal Physiol Country: United States |
Other Details:
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Languages: eng Pagination: F831-8 Citation Subset: IM |
Affiliation:
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Division of Physiology, Department of Physiology and Medical Physics, Innsbruck Medical University, Innsbruck, Austria. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aging
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drug effects Apoptosis / drug effects Cell Line Cyclosporine / adverse effects* DNA / biosynthesis Dose-Response Relationship, Drug Epithelial Cells / cytology, drug effects*, metabolism* Humans Kidney Tubules / cytology* Necrosis RNA, Messenger / genetics Time Factors |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; 59865-13-3/Cyclosporine; 9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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