| High glucose promotes nascent nephron apoptosis via NF-kappaB and p53 pathways. | |
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MedLine Citation:
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PMID: 20962117 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A hyperglycemic environment in utero reduces kidney size and nephron number due to nascent nephron apoptosis. However, the underlying mechanisms are incompletely understood. The present study investigated whether the nascent nephron apoptosis promoted by high glucose is mediated via the transcription factor NF-κB and p53 signaling pathways. Neonatal mouse kidneys from the offspring of nondiabetic, diabetic, and insulin-treated diabetic dams were used for in vivo studies, and MK4 cells, an embryonic metanephric mesenchymal (MM) cell line, were used for in vitro studies. Neonatal kidneys of the offspring of diabetic mothers exhibited an increased number of apoptotic cells and reactive oxygen species (ROS) generation, enhanced NF-κB activation, and nuclear translocation of its subunits (p50 and p65 subunits) as well as phosphorylation (Ser 15) of p53 compared with kidneys of offspring of nondiabetic mothers. Insulin treatment of diabetic dams normalized these parameters in the offspring. In vitro, high-glucose (25 mM) induced ROS generation and significantly increased MK4 cell apoptosis and caspase-3 activity via activation of NF-κB pathway, with p53 phosphorylation and nuclear translocation compared with normal glucose (5 mM). These changes in a high-glucose milieu were prevented by transient transfection of small interfering RNAs for dominant negative IκBα or IKK or p53. Our data demonstrate that high glucose-induced nascent nephron apoptosis is mediated, at least in part, via ROS generation and the activation of NF-κB and p53 pathways. |
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Authors:
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Yun-Wen Chen; Isabelle Chenier; Shiao-Ying Chang; Stella Tran; Julie R Ingelfinger; Shao-Ling Zhang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-20 |
Journal Detail:
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Title: American journal of physiology. Renal physiology Volume: 300 ISSN: 1522-1466 ISO Abbreviation: Am. J. Physiol. Renal Physiol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-07 Completed Date: 2011-02-09 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: F147-56 Citation Subset: IM |
Affiliation:
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Université de Montréal, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, CRCHUM, Hôpital Hôtel-Dieu, Pavillon Masson, 3850 Saint-Urbain St., Montreal, Quebec, Canada H2W 1T7. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects* Cell Line Diabetes Mellitus, Experimental / physiopathology* Female Glucose / administration & dosage, pharmacology* Insulin / therapeutic use Kidney / abnormalities Mice NF-kappa B / physiology* NF-kappa B p50 Subunit / biosynthesis Nephrons / abnormalities, drug effects* Pregnancy Pregnancy in Diabetics / drug therapy, physiopathology Transcription Factor RelA / biosynthesis Tumor Suppressor Protein p53 / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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MOP86450//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/NF-kappa B; 0/NF-kappa B p50 Subunit; 0/Transcription Factor RelA; 0/Tumor Suppressor Protein p53; 11061-68-0/Insulin; 50-99-7/Glucose |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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