Files and links (1)
Shi_Leng-Chu_19975.05 MB
PDF Restricted Access, VIEWABLE UPON REQUEST: contact archives@drexel.edu
Dissertation
Platelet activating factor receptor(s) mediates cell death induced by "Ischemia-reperfusion" in an hippocampal cell line
Doctor of Philosophy (Ph.D.), Allegheny University of the Health Sciences
May 1997
DOI:
https://doi.org/10.17918/00007875
Abstract
Mild ischemic/hypoxic insult produces delayed neuronal damage in many brain areas which may undergo apoptosis. A phospholipid, PAF, is thought to mediate neuronal damage produced by ischemia/reperfusion, PAF production and metabolism are increased by ischemic/hypoxic lesion, and PAF antagonists are shown to protect neuronal damage. However, the molecular mechanism of PAF action on the neurons subjected to hypoxic/ischemic insult is unclear because of the heterogeneity of brain. Therefore, the possible role of PAF receptor(s) in the ischemia/reperfusion was examined in order to further our knowledge concerning the underlying mechanisms of neuronal damage due to ischemic/hypoxic insult. Specifically, experiments were designed to investigate the effects of hypoxia/hypoglycemia in a hippocampus-derived cell line, HN33.11 cells, a cell line which exhibits PAF-stimulated PI metabolism via Gq and Gi proteins on (1) the role of PAF receptors in cell death due to hypoxia/ hypoglycemia and (2) functions of PAF receptor-coupled G proteins in mediating cellular damage during hypoxic insult. A delayed cell death with apoptotic features was observed when cells were treated with hypoxia/hypoglycemia condition (ischemia) followed by incubation in normal control medium (reperfusion). PAF produced in the early reperfusion elicited cellular death which was inhibited by PAF receptor antagonists. The PAF receptor-elicited intracellular Ca²⁺ increase may mediate the PAF action during reperfusion. Treatment with pertussis toxin increased cellular damage induced by ischemia/reperfusion. PTX treatment also potentiated cell death induced by the PAF analogue. On the other hand, G[alpha]q antisense treatment protected cells from ischemia/reperfusion induced cell death by decreasing G[alpha]q protein levels. Moreover, this treatment also attenuated MC-PAF-induced cell death during ischemia/reperfusion. In conclusion, hypoxia/hypoglycemia in HN33.11 cells induces a delayed cell death via apoptosis; this is mediated by a delayed increase in PAF production and activation of PAF receptor. Gq and Gi proteins, which are functionally coupled to PAF receptor(s), play antagonistic roles in PAF receptor mediated ischemia/ reperfusion-induced cellular damage. The predominant coupling between PAF receptor and Gq may underlie the injury induced by ischemia/reperfusion in HN33.11 cells.
Metrics
10 Record Views
Details
- Title
- Platelet activating factor receptor(s) mediates cell death induced by "Ischemia-reperfusion" in an hippocampal cell line
- Creators
- Leng-Chu Shi
- Contributors
- Eitan Friedman (Advisor) - Drexel University, Allegheny University of the Health Sciences (1996-1998)
- Awarding Institution
- Allegheny University of the Health Sciences
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Allegheny University of the Health Sciences; Philadelphia, Pennsylvania
- Number of pages
- ix, 126 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Pharmacology [Historical]; Allegheny University of the Health Sciences (1996-1998); School of Medicine (1996-1998)
- Other Identifier
- 991021888766204721