Journal article
Involvement of Platelet‐Activating Factor in Cell Death Induced Under Ischemia/Postischemia‐Like Conditions in an Immortalized Hippocampal Cell Line
Journal of neurochemistry, v 70(3), pp 1035-1044
Mar 1998
PMID: 9489723
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
: 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 µM 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.
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Details
- Title
- Involvement of Platelet‐Activating Factor in Cell Death Induced Under Ischemia/Postischemia‐Like Conditions in an Immortalized Hippocampal Cell Line
- Creators
- Leng‐Chu Shi - Allegheny University of the Health SciencesHoau‐Yan WangEitan Friedman - Allegheny University of the Health Sciences
- Publication Details
- Journal of neurochemistry, v 70(3), pp 1035-1044
- Publisher
- Blackwell Science Ltd
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000072132700017
- Scopus ID
- 2-s2.0-0031892137
- Other Identifier
- 991019169903604721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemistry & Molecular Biology
- Neurosciences