Document Detail


Altered lipid raft composition and defective cell death signal transduction in glycosylphosphatidylinositol anchor-deficient PIG-A mutant cells.
MedLine Citation:
PMID:  18544084     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Paroxysmal nocturnal haemoglobinuria (PNH) is a clonal disorder of haematopoietic stem cells caused by somatic PIGA mutations, resulting in a deficiency in glycosylphosphatidylinositol-anchored proteins (GPI-AP). Because GPI-AP associate with lipid rafts (LR), lack of GPI-AP on PNH cells may result in alterations in LR-dependent signalling. Conversely, PNH cells are a suitable model for investigating LR biology. LR from paired, wild-type GPI(+), and mutant GPI(-) cell lines (K562 and TF1) were isolated and analysed; GPI(-) LR contained important anti-apoptotic proteins, not found in LR from GPI(+) cells. When methyl-beta-cyclodextrin (MbetaCD) was utilized to probe for functional differences between normal and GPI(-) LR, increased levels of phospho-p38 mitogen-activated protein kinase (MAPK), and phospho-p65 nuclear factor NF-kappaB were found in control and GPI(-) cells respectively. Subsequent experiments addressing the inhibition of phosphoinositide-3-kinase (PI3K) suggest that the PI3K/AKT pathway may be responsible for the resistance of K562 GPI(-)cells to negative effects of MbetaCD. In addition, transduction of tumour necrosis factor-alpha (TNF-alpha) signals in a LR-dependent fashion increased induction of p38 MAPK in GPI(+) and increased pro-survival NF-kappaB levels in K562 GPI(-) cells. Therefore, we suggest that the altered LR-dependent signalling in PNH-like cells may induce different responses to pro-inflammatory cytokines from those observed in cells with intact GPI-AP.
Authors:
Hadrian Szpurka; Andrew E Schade; Anna M Jankowska; Jaroslaw P Maciejewski
Related Documents :
16391234 - Cyclooxygenase-1-derived pge2 promotes cell motility via the g-protein-coupled ep4 rece...
20308364 - A novel rac-dependent checkpoint in b cell development controls entry into the splenic ...
20117834 - Cell-laden microwells for the study of multicellularity in lymphocyte fate decisions.
10654604 - Ultrabithorax and the control of cell morphology in drosophila halteres.
9585084 - Bcl-2 expression does not not correlate with patient outcome in pediatric acute myeloge...
17124554 - A synthetic uracil derivative with antitumor activity through decreasing cyclin d1 and ...
Publication Detail:
Type:  Journal Article     Date:  2008-06-09
Journal Detail:
Title:  British journal of haematology     Volume:  142     ISSN:  1365-2141     ISO Abbreviation:  Br. J. Haematol.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2009-03-16     Completed Date:  2009-05-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372544     Medline TA:  Br J Haematol     Country:  England    
Other Details:
Languages:  eng     Pagination:  413-22     Citation Subset:  IM    
Affiliation:
Experimental Haematology and Haematopoiesis Section, Taussig Cancer Centre, Cleveland Clinic, Cleveland, OH 44195, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / metabolism
Apoptosis / drug effects
Cell Line
Cytokines / metabolism,  pharmacology
Electrophoresis, Gel, Two-Dimensional
Glycosylphosphatidylinositols / deficiency*,  genetics,  metabolism
Hematopoietic Stem Cells / metabolism*,  pathology
Hemoglobinuria, Paroxysmal / genetics,  immunology,  metabolism*,  pathology
Humans
Membrane Microdomains / metabolism*
Membrane Proteins / genetics*
Mutation*
Signal Transduction
Tandem Mass Spectrometry
Chemical
Reg. No./Substance:
0/Cytokines; 0/Glycosylphosphatidylinositols; 0/Membrane Proteins; 0/phosphatidylinositol glycan-class A protein; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase

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


Previous Document:  p-Coumaric acid, a constituent of Sasa quelpaertensis Nakai, inhibits cellular melanogenesis stimula...
Next Document:  A requirement for calcium in the caspase-independent killing of Burkitt lymphoma cell lines by Ritux...