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Current Topics in Biochemical Research   Volumes    Volume 3 
Abstract
Implications for the identification of BCL-2 anti-apoptosis genes in the pathogenesis of ischaemic acute renal failure
Glenda C. Gobe, Zoltan H. Endre
Pages: 91 - 100
Number of pages: 10
Current Topics in Biochemical Research
Volume 3 

Copyright © 2000 Research Trends. All rights reserved

ABSTRACT

The molecular pathways involved in initiation and commitment of renal tubular epithelial cells to apoptosis after ischaemic acute renal failure (IARF) are not well-defined. The choice that a cell makes between survival or death involves, amongst many other cellular controls, signal transduction pathways and genes known to modulate apoptosis. During IARF, anti-apoptotic Bcl-2 proteins protect damaged distal tubules in which only moderate levels of apoptosis are found. In comparison, Bax is upregulated in the proximal tubules where cell death tends to manifest as necrosis and apoptosis. An intricate inter-relationship between growth factors synthesised in the protected distal tubule and distal-to-proximal cell cross talk for protection or repair of the proximal nephron segment is now apparent. Related in vitro experiments have verified the interrelationship between the anti-apoptotic Bcl-2 proteins and growth factors such as epidermal growth factor (EGF), in making renal distal cells resistant to IARF-induced injury. Mechanisms of action include the translocation of anti-apoptotic Bcl-2 proteins to the mitochondria in ischaemia-stressed renal cells and the development of complexes between anti-apoptotic Bcl-2 proteins and signal transduction molecules normally known to be associated with EGF receptor activation or oxidative stress. Further definition of these survival messages will give greater scope to devising new methods of minimising renal injury in IARF.

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