Effect of hexadecylglycerol supplementation on protein kinase C-mediated signaling pathways in a murine macrophage-like cell line

Date
2005
DOI
Authors
Karthik, A.G.
Version
Embargo Date
Indefinite
OA Version
Citation
Abstract
All mammalian membranes contain ether-linked glycerolipids in which the sn-1 position of the glycerol backbone is occupied by an alkyl chain attached through either an ether, or vinyl ether linkage (plasmalogens). Plasmalogens and ether lipids have been implicated in important cellular functions such as (i) mediating membrane-fusion events, (ii) serving as endogenous antioxidants and (iii) modulating protein kinase C (PKC) and/or phosphatidylinositol-3-kinase (PI3-K)-mediated cellular responses to stimuli. sn -1-hexadecylglycerol (HG) is a simple ether lipid precursor that is able to enter cells and then enter the biosynthetic pathway for ether lipids. We have used HG and ether lipid-deficient animal cell mutants to examine ether lipids' cellular roles. We have examined three cellular events thought to be influenced by cellular ether lipid levels and mediated by both PKC and PI3-K, namely, the generation of superoxide anion (respiratory burst), the release of arachidonic acid (AA) and fragment crystallizable γ (Fcγ) receptor-mediated phagocytosis, three processes essential for neutrophil and macrophage immune functions. When the ether lipid-deficient murine macrophage-like cell line, RAW.108, was treated with HG prior to simulation, superoxide production in response to either a soluble stimulus (phorbol ester, PMA) or particulate stimulus (zymosan), was reduced by >90%. HG supplementation also inhibited PMA-induced but not zymosan-induced AA release, suggesting that two different pathways exist for the release of AA in these cells depending on the stimulus. Fcγ receptor-mediated phagocytosis was also inhibited by HG supplementation. This inhibition was not related to changes in plasmalogen levels as HG was also effective in inhibiting the respiratory burst in the mutant cell line, RAW.12, which cannot form plasmalogens even with HG supplementation. The mechanism of inhibition of these events by HG was likely due to inhibition of PKC and not PI3-K, which was verified independently using other inhibitors of these enzymes.
Description
Thesis (Ph.D.)--Boston University
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.
License