Please use this identifier to cite or link to this item:
Title: Characterisation of neuropathy target esterase in mammalian cells
Authors: Rezaie, Nima
Award date: 2005
Presented at: University of Leicester
Abstract: The present study found that NTE's catalytic activity is not regulated by cAMP. Purification of the R domain could not be achieved as the recombinant polypeptide is essentially insoluble and consequently, direct cAMP binding could not be attempted. The reduction of NTE activity in HeLa cells caused inhibition of GroPCho production without altering PtdCho levels. Conversely, the inducible overexpression of NTE in a stable HeLa cell line resulted in increased GroPCho production also without altering PtdCho levels. Treatment of HeLa cells with ether-linked lipids caused an apparent inhibition of PtdCho synthesis followed by a time- and concentration-dependent cytotoxicity that was not altered by the inducible overexpression of NTE. Several mouse tissues were screened and the highest NTE expression was found in kidney tubular epithelial cells. Tubular epithelial cells from NTE heterozygous (HZ) mutant mice demonstrated the same GroPCho and phospholipids levels as wild-type cells, despite a 40% lower NTE PV hydrolase activity. The NTE HZ cells had 65% the CDP-choline levels of wild-type cells suggesting a down-regulation of PtdCho synthesis. Greater reduction of NTE activity by treating wild-type tubular epithelial cells with mipafox resulted in a 90% reduction in GroPCho production also accompanied by a down-regulation of PtdCho synthesis. In conclusion, changes in NTE activity, in both cell types, are compensated by corresponding changes in PtdCho synthesis to maintain phospholipids homeostasis.
Type: Thesis
Level: Doctoral
Qualification: PhD
Rights: Copyright © the author. All rights reserved.
Appears in Collections:Theses, MRC Toxicology Unit
Leicester Theses

Files in This Item:
File Description SizeFormat 
U217378.pdf12.17 MBAdobe PDFView/Open

Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.