Document Detail

Involvement of platelet-activating factor in cell death induced under ischemia/postischemia-like conditions in an immortalized hippocampal cell line.
MedLine Citation:
PMID:  9489723     Owner:  NLM     Status:  MEDLINE    
The involvement of platelet-activating factor (PAF) in cell damage induced by ischemia/postischemia-like conditions was studied in a hippocampus-derived cell line, HN33.11. Cells exposed to N2-saturated glucose-free HEPES-buffered saline (ischemia) for 5 h followed by 18 h of incubation in serum-free control medium (postischemia reincubation) remained 67.4 +/- 2.4% viable in comparison with sham-treated cells. Analysis of DNA fragmentation in combination with Hoechst 33258 staining indicates that apoptosis is the dominant mode of cell death in the present model. PAF level during 10 h of ischemia was unchanged. However, an increase in PAF accumulation was found early during the reincubation period that followed 5 h of ischemia. Peak PAF concentrations were noted at 2 h after initiation of reincubation and rapidly declined to control level after 7 h of reincubation. Consistent with a role of PAF in mediating cell death under ischemia/postischemia reincubation in this model, the PAF antagonist BN 50739 exerted a dose-dependent protective effect. Maximal protection (85.7 +/- 5.4%) of the cells from ischemia/reincubation-induced cell damage was achieved at 0.1 microM BN 50739. The PAF antagonist lacked any protective effect against ischemia-induced cell death. On the other hand, the addition of the stable PAF analogue 1-O-hexadecyl-2-N-methylcarbamyl-sn-glycero-3-phosphocholine (MC-PAF) at the onset of ischemia potentiated ischemia/reincubation-induced apoptosis--an effect that was blocked by BN 50739. Pretreatment of HN33.11 cells with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid acetoxymethyl ester (BAPTA-AM) also provided a protective effect against ischemia/reincubation-induced cell damage. BAPTA-AM increased cell viability by 50%. Pretreatment with BAPTA-AM also decreased ischemia/reincubation-induced PAF accumulation in HN33.11 cells. The results suggest that PAF, acting via a PAF receptor, is at least in part mediating apoptosis under ischemia/postischemia-like conditions in HN33.11 cells.
L C Shi; H Y Wang; E Friedman
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  70     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  1998 Mar 
Date Detail:
Created Date:  1998-03-12     Completed Date:  1998-03-12     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1035-44     Citation Subset:  IM    
Department of Pharmacology, MCP-Hahnemann School of Medicine, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania 19129, USA.
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MeSH Terms
Azepines / pharmacology
Calcium / physiology
Cell Death / physiology
Cell Line, Transformed
Dizocilpine Maleate / pharmacology
Excitatory Amino Acid Antagonists / pharmacology
Hippocampus / blood supply,  chemistry,  cytology*
Ischemia / physiopathology*
Platelet Activating Factor / analysis,  physiology*
Platelet Membrane Glycoproteins / antagonists & inhibitors
Pyridinium Compounds / pharmacology
Receptors, Cell Surface*
Receptors, G-Protein-Coupled*
Reperfusion Injury / physiopathology
Signal Transduction / drug effects,  physiology
Triazoles / pharmacology
Reg. No./Substance:
0/Azepines; 0/Excitatory Amino Acid Antagonists; 0/Platelet Activating Factor; 0/Platelet Membrane Glycoproteins; 0/Pyridinium Compounds; 0/Receptors, Cell Surface; 0/Receptors, G-Protein-Coupled; 0/Triazoles; 0/platelet activating factor receptor; 100488-87-7/CV 6209; 128672-07-1/BN 50739; 7440-70-2/Calcium; 77086-22-7/Dizocilpine Maleate

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