The subcellular localization, fate and handling of cardiac glycosides by HeLa cells

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" The subcellular localization, fate and handling of cardiac glycosides by HeLa cells "
Al-Gharably, Naji Mohammed Lamb, J. F.

Document Type	:	Latin Dissertation
Record Number	:	828636
Doc. No	:	TLets373017
Main Entry	:	Al-Gharably, Naji Mohammed
Title & Author	:	The subcellular localization, fate and handling of cardiac glycosides by HeLa cells\ Al-Gharably, Naji MohammedLamb, J. F.
College	:	University of St Andrews
Date	:	1986
student score	:	1986
Degree	:	Thesis (Ph.D.)
Abstract	:	The subcellular fate of ouabain digoxin and digitoxin after binding to HeLa cell surface was studied using a conventional ultracentrifugation technique, Ouabain, digoxin and digitoxin codistributed with the plasma membrane marker 5'-nucleotidase immediately after bindings and cells chilled at 2°C for 24 hours retained ouabain in the plasma membrane fractions with time these glycosides are internalized to a subcellular compartment apparently the lysosomes. Internalized ouabain showed a distribution pattern throughout the linear sucrose gradient which was similar to that of the lysosomal marker B-hexosaminidase and both activity were dependent on lysosomal integrity by showing similar response to shearing forceo Internalized digoxin although showed a peak of activity in the same fraction as the lysosomal marker, but its sedimentability was insensitive to shear. Both ouabain and digoxin also responded differently to chloroquine. Chloroquine slightly reduced the accumulation of ouabain by HeLa cells, but did not much alter its excretion rate. On the other hand the amount of digoxin retained by the cell depends on the lysosomal activity. Chloroquine which reduces the lysosomal enzyme activity and inhibits lysosomal degradation result in larger accumulation of digoxin by the cell. Antitubular agents (vinblastine and nocodazol), were found to have no detectable effect on the excretion rate of ouabains while the excretion rate of digoxin was reduced by vinblastine. The results are consistent with a process of internalization and turnover of sodium pumps by HeLa cells through receptor mediated endocytosis. The lipophilic property of digoxin seems to account for the differences between ouabain and digoxin handling by HeLa cells.
Subject	:	QP702.G59G2 ; Glycosides
Added Entry	:	Lamb, J. F.
Added Entry	:	University of St Andrews