T lymphocyte nuclear diacylglycerol is derived from both de novo synthesis and phosphoinositide hydrolysis
T lymphocyte nuclear diacylglycerol is derived from both de novo synthesis and phosphoinositide hydrolysis
Novel phospholipid metabolism in T lymphocytes and the generation of biologically active lipid second messengers (LSMs) has attracted much attention in recent years. Despite this interest, no reports have attempted to characterise such events in the nuclei of these cells. In order to gain insight into the structural relationships between the lipids diglyceride (DG) and phosphatidic acid (PtdOH) and their structural precursors phosphatidylcholine (PtdCho) and phosphatidylinositides (PtdIns) in the nuclei of CTLL-2 T lymphocytes, an analysis of their molecular species was performed. The results clearly indicated that there were two pools of DG. The major pool consisted primarily of saturated and monunsaturated structures whereas the minor pool consisted of more unsaturated species, most likely derived from PtdIns. Only the latter pool was found to be accessible to endogenous nuclear diacylglycerol kinase (DGK) activity which showed partial inhibition with the recognised DGK inhibitor R59949. Molecular species analysis of the endogenous nuclear PtdOH revealed it to be distinct from that generated by the endogenous DGK, but instead resembled that of PtdCho species. We were unable to detect enzymatic activities which targeted PtdCho (PtdCho-phospholipase C (PtdCho-PLC), PtdCho-phospholipase D (PtdCho-PLD) and sphingomyelin synthase (SMS)) but instead a detectable PtdOH phosphatase (PAP) activity. We propose that, in exponentially growing CTLL-2 cells, synthesis de novo represents one of the routes for the biosynthesis of structural phospholipids which may be the source of biologically active LSMs in the nucleus.
Adenosine Triphosphate/metabolism Animals Cell Fractionation Cell Line Cell Nucleus/enzymology/*metabolism Diacylglycerol Kinase/antagonists & inhibitors/metabolism Diglycerides/chemistry/*metabolism Fluorescent Dyes/metabolism Lipolysis Mice Phosphatidic Acids/chemistry/metabolism Phosphatidylcholines/chemistry Phosphatidylinositols/chemistry/*metabolism T-Lymphocytes/drug effects/*metabolism
158-168
Jones, D. R.
fcbc07f0-6ce7-4ea0-b8b3-f0e6a9581279
D'Santos, C. S.
544f8e9e-95e1-4d0b-9a72-312afe893eb3
Merida, I.
02c183b0-ed28-47cb-83ac-90f69e6a973d
Divecha, N.
5c2ad0f8-4ce7-405f-8a15-2fc4ab96d787
17 January 2002
Jones, D. R.
fcbc07f0-6ce7-4ea0-b8b3-f0e6a9581279
D'Santos, C. S.
544f8e9e-95e1-4d0b-9a72-312afe893eb3
Merida, I.
02c183b0-ed28-47cb-83ac-90f69e6a973d
Divecha, N.
5c2ad0f8-4ce7-405f-8a15-2fc4ab96d787
Jones, D. R., D'Santos, C. S., Merida, I. and Divecha, N.
(2002)
T lymphocyte nuclear diacylglycerol is derived from both de novo synthesis and phosphoinositide hydrolysis.
The International Journal of Biochemistry & Cell Biology, 34 (2), .
(doi:10.1016/s1357-2725(01)00108-x).
Abstract
Novel phospholipid metabolism in T lymphocytes and the generation of biologically active lipid second messengers (LSMs) has attracted much attention in recent years. Despite this interest, no reports have attempted to characterise such events in the nuclei of these cells. In order to gain insight into the structural relationships between the lipids diglyceride (DG) and phosphatidic acid (PtdOH) and their structural precursors phosphatidylcholine (PtdCho) and phosphatidylinositides (PtdIns) in the nuclei of CTLL-2 T lymphocytes, an analysis of their molecular species was performed. The results clearly indicated that there were two pools of DG. The major pool consisted primarily of saturated and monunsaturated structures whereas the minor pool consisted of more unsaturated species, most likely derived from PtdIns. Only the latter pool was found to be accessible to endogenous nuclear diacylglycerol kinase (DGK) activity which showed partial inhibition with the recognised DGK inhibitor R59949. Molecular species analysis of the endogenous nuclear PtdOH revealed it to be distinct from that generated by the endogenous DGK, but instead resembled that of PtdCho species. We were unable to detect enzymatic activities which targeted PtdCho (PtdCho-phospholipase C (PtdCho-PLC), PtdCho-phospholipase D (PtdCho-PLD) and sphingomyelin synthase (SMS)) but instead a detectable PtdOH phosphatase (PAP) activity. We propose that, in exponentially growing CTLL-2 cells, synthesis de novo represents one of the routes for the biosynthesis of structural phospholipids which may be the source of biologically active LSMs in the nucleus.
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Published date: 17 January 2002
Additional Information:
Jones, David R D'Santos, Clive S Merida, Isabel Divecha, Nullin eng Research Support, Non-U.S. Gov't Netherlands 2002/01/26 Int J Biochem Cell Biol. 2002 Feb;34(2):158-68. doi: 10.1016/s1357-2725(01)00108-x.
Keywords:
Adenosine Triphosphate/metabolism Animals Cell Fractionation Cell Line Cell Nucleus/enzymology/*metabolism Diacylglycerol Kinase/antagonists & inhibitors/metabolism Diglycerides/chemistry/*metabolism Fluorescent Dyes/metabolism Lipolysis Mice Phosphatidic Acids/chemistry/metabolism Phosphatidylcholines/chemistry Phosphatidylinositols/chemistry/*metabolism T-Lymphocytes/drug effects/*metabolism
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Local EPrints ID: 480158
URI: http://eprints.soton.ac.uk/id/eprint/480158
ISSN: 1357-2725
PURE UUID: bad6ae7b-25b3-4dd3-becd-2791c65ed80a
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Date deposited: 01 Aug 2023 16:55
Last modified: 17 Mar 2024 02:59
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Author:
D. R. Jones
Author:
C. S. D'Santos
Author:
I. Merida
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