Document Detail

Caspase-3-Independent Internucleosomal DNA Fragmentation in Ischemic Acute Kidney Injury.
MedLine Citation:
PMID:  22678593     Owner:  NLM     Status:  Publisher    
Background/Aims: Renal tubular cell death in ischemia-reperfusion does not follow the classical apoptosis or necrosis phenotype. We characterized the morphological and biochemical features of injured tubular epithelial cells in ischemic acute kidney injury (AKI). Methods: Ischemic AKI was induced in rats by 60 min of ischemia followed by 24 h of reperfusion. Light and electron microscopic TUNEL (LM-TUNEL and EM-TUNEL), gel electrophoresis of extracted DNA, and caspase-3 involvement were examined during the development of death. Results: Damaged tubular epithelial cells with condensed and LM-TUNEL-positive (+) nuclei were prominent at 12 and 18 h after reperfusion with DNA 'ladder' pattern on gel electrophoresis. EM-TUNEL+ cells were characterized by nuclei with condensed and clumping chromatin, whereas the cytoplasm showed irreversible necrosis. The protein levels and activity of caspase-3 did not increase in kidneys after reperfusion. In addition, caspase inhibitor (ZVAD-fmk) failed to inhibit DNA fragmentation and prevent tubular epithelial cell death in ischemic AKI. Conclusion: Caspase-3-independent internucleosomal DNA fragmentation occurs in injured tubular epithelial cells undergoing irreversible necrosis in ischemic AKI. The manner of this cell death may be identical to the cell death termed apoptotic necrosis, aponecrosis, or necrapoptosis. Ischemia-reperfusion injury activates caspase-3-independent endonuclease, which in turn induces irreversible damage of tubular epithelial cells, and may contribute to the initiation and development of AKI.
Taiko Yoshida; Akira Shimizu; Yukinari Masuda; Akiko Mii; Emiko Fujita; Kaoru Yoshizaki; Seiichiro Higo; Go Kanzaki; Yusuke Kajimoto; Hideki Takano; Yuh Fukuda
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-05
Journal Detail:
Title:  Nephron. Experimental nephrology     Volume:  120     ISSN:  1660-2129     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101159770     Medline TA:  Nephron Exp Nephrol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  e103-e113     Citation Subset:  -    
Copyright Information:
Copyright © 2012 S. Karger AG, Basel.
Department of Pathology (Analytic Human Pathology), Nippon Medical School, Tokyo, Japan.
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