Journal of the American Society of Nephrology
2007 JASN IMPACT FACTOR 7.111 HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP 
    advanced
CURRENT ISSUE ARCHIVES JASN Express ONLINE SUBMISSION


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by YANG, B.
Right arrow Articles by NAHAS, A. M. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by YANG, B.
Right arrow Articles by NAHAS, A. M. E.
J Am Soc Nephrol 12:485-495, 2001
© 2001 American Society of Nephrology

Apoptosis and Caspase-3 in Experimental Anti-Glomerular Basement Membrane Nephritis

BIN YANG*, TIMOTHY S. JOHNSON*, GRAHAM L. THOMAS*, PHILIP F. WATSON{dagger}, BART WAGNER{ddagger} and A. MEGUID EL NAHAS*

* Sheffield Kidney Institute, Northern General Hospital Trust, Sheffield, United Kingdom.
{dagger} Sheffield University Division of Clinical Sciences, Northern General Hospital Trust, Sheffield, United Kingdom.
{ddagger} Department of Histopathology, Northern General Hospital Trust, Sheffield, United Kingdom.

Correspondence to Dr. Tim Johnson, Sheffield Kidney Institute, Northern General Hospital, Herries Road, Sheffield S5 7AU, England, United Kingdom. Phone: 44-0-114-271-5322; Fax: 44-0-114-271-4410; E-mail: T.Johnson{at}Sheffield.ac.uk

Abstract. The caspase family is central to the proteolytic events of apoptosis. In particular, caspase-3 plays a key role in the execution of apoptosis. However, the importance of caspase-3 in renal cell apoptosis during kidney scarring has not been established. Here, nephrotoxic nephritis (NTN) was induced in Wistar Kyoto rats by a single intravenous injection of rabbit anti-rat glomerular basement membrane serum, with analysis at days 7, 15, 30, and 45 after injection. Cell apoptosis (in situ end labeling of DNA, light and electron microscopy), proliferation (proliferating cell nuclear antigen-positive cells), and inflammation (ED1-positive cells) all increased in NTN kidneys, peaking early (day 7) in the glomeruli and later (days 30 to 45) in the tubules and interstititum. The expression of caspase-3 mRNA (Northern blotting) was increased in NTN kidneys on days 7, 30, and 45 (173.3%, 228%, and 241.7%, respectively; P < 0.05). Western blotting showed that a 24-kD protein band (caspase-3 active subunit) increased with time in NTN kidneys (P < 0.01) and reached a maximum on day 45 (6.08-fold increase). A 32 kD band (caspase-3 precursor) was also increased on day 45 (3.92-fold; P < 0.01). Elevated caspase-3 activity (two- to threefold) was observed in NTN kidneys at all time points (P < 0.01). Upregulated expression of caspase-3 at all levels positively correlated with apoptosis, whereas both correlated closely with inflammation, proliferation, and subsequent fibrosis in glomeruli, tubules, and interstitium (P < 0.05). Inhibition of caspase-3 during the course of experimental nephritis may offer a new therapeutic approach for the prevention of renal apoptosis and the associated renal tubular atrophy and fibrosis.




This article has been cited by other articles:


Home page
 Nephrol Dial TransplantHome page
C. M. Turner, F. W. K. Tam, P.-C. Lai, R. M. Tarzi, G. Burnstock, C. D. Pusey, H. T. Cook, and R. J. Unwin
Increased expression of the pro-apoptotic ATP-sensitive P2X7 receptor in experimental and human glomerulonephritis
Nephrol. Dial. Transplant., February 1, 2007; 22(2): 386 - 395.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
N. Tejera, D. Gomez-Garre, A. Lazaro, J. Gallego-Delgado, C. Alonso, J. Blanco, A. Ortiz, and J. Egido
Persistent Proteinuria Up-Regulates Angiotensin II Type 2 Receptor and Induces Apoptosis in Proximal Tubular Cells
Am. J. Pathol., May 1, 2004; 164(5): 1817 - 1826.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
S. Cardin, D. Li, N. Thorin-Trescases, T.-K. Leung, E. Thorin, and S. Nattel
Evolution of the atrial fibrillation substrate in experimental congestive heart failure: angiotensin-dependent and -independent pathways
Cardiovasc Res, November 1, 2003; 60(2): 315 - 325.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
J. Rossert, B. Fouqueray, and J. J. Boffa
Anemia Management and the Delay of Chronic Renal Failure Progression
J. Am. Soc. Nephrol., July 1, 2003; 14(90002): S173 - 177.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
F. Li, H. P. Mao, K. L. Ruchalski, Y. H. Wang, W. Choy, J. H. Schwartz, and S. C. Borkan
Heat stress prevents mitochondrial injury in ATP-depleted renal epithelial cells
Am J Physiol Cell Physiol, September 1, 2002; 283(3): C917 - C926.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
J. Rossert, W. M. McClellan, S. D. Roger, and D. L. Verbeelen
Epoetin treatment: what are the arguments to expect a beneficial effect on renal disease progression?
Nephrol. Dial. Transplant., March 1, 2002; 17(3): 359 - 362.
[Full Text] [PDF]


HOME CURRENT ISSUE ARCHIVES JASN Express ONLINE SUBMISSION AUTHOR INFO
EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673