Document Detail


Induction of vanadium accumulation and nuclear sequestration causing cell suicide in human Chang liver cells.
MedLine Citation:
PMID:  8774748     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Very little is known about the modulation of vanadium accumulation in cells, although this ultratrace element has long been seen as an essential nutrient in lower life forms, but not necessarily in humans where factors modulating cellular uptake of vanadium seem unclear. Using nuclear microscopy, which is capable of the direct evaluation of free and bound (total) elemental concentrations of single cells we show here that an NH4Cl acidification prepulse causes distinctive accumulation of vanadium (free and bound) in human Chang liver cells, concentrating particularly in the nucleus. Vanadium loaded with acidification but leaked away with realkalinization, suggests proton-dependent loading. Vanadyl(4), the oxidative state of intracellular vanadium ions, is known to be a potent source of hydroxyl free radicals (OH). The high oxidative state of nuclei after induction of vanadyl(4) loading was shown by the redox indicator methylene blue, suggesting direct oxidative damage to nuclear DNA. Flow cytometric evaluation of cell cycle phase-specific DNA composition showed degradation of both 2N and 4N DNA phases in G1, S and G2/M cell cycle profiles to a solitary IN DNA peak, in a dose-dependent manner, effective from micromolar vanadyl(4) levels. This trend was reproduced with microccocal nuclease digestion in a time response, supporting the notion of DNA fragmentation effects. Several other approaches confirmed fragmentation occurring in virtually all cells after 4mM V(4) loading. Ultrastructural profiles showed various stages of autophagic autodigestion and well defined plasma membrane outlines, consistent with programmed cell death but not with necrotic cell death. Direct intranuclear oxidative damage seemed associated with the induction of mass suicide in these human Chang liver cells following vanadium loading and nuclear sequestration.
Authors:
K H Sit; R Paramanantham; B H Bay; K P Wong; P Thong; F Watt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experientia     Volume:  52     ISSN:  0014-4754     ISO Abbreviation:  Experientia     Publication Date:  1996 Aug 
Date Detail:
Created Date:  1996-10-03     Completed Date:  1996-10-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376547     Medline TA:  Experientia     Country:  SWITZERLAND    
Other Details:
Languages:  eng     Pagination:  778-85     Citation Subset:  IM    
Affiliation:
Department of Anatomy, National University of Singapore, Kent Ridge, Singapore.
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MeSH Terms
Descriptor/Qualifier:
Ammonium Chloride / metabolism,  pharmacology
Apoptosis / drug effects*
Cell Line
Cell Nucleus / metabolism*
DNA / metabolism
DNA Damage
Flow Cytometry
Fluoresceins / metabolism
Fluorescent Dyes / metabolism
Humans
Hydrogen-Ion Concentration
Hydroxyl Radical / metabolism
Liver / cytology*,  drug effects,  metabolism,  ultrastructure
Methylene Blue / metabolism
Micrococcal Nuclease / metabolism
Microscopy
Spectrometry, Fluorescence
Vanadium / metabolism*,  pharmacology*
X-Rays
Chemical
Reg. No./Substance:
0/Fluoresceins; 0/Fluorescent Dyes; 12125-02-9/Ammonium Chloride; 3352-57-6/Hydroxyl Radical; 61-73-4/Methylene Blue; 7440-62-2/Vanadium; 85138-49-4/2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; 9007-49-2/DNA; EC 3.1.31.1/Micrococcal Nuclease

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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