Relationship between enhanced turnover of phosphatidylinositol and lymphocyte activation by mitogens

Maino, Vernon C.; Hayman, Michael J.; Crumpton, Michaël J.

doi:10.1042/bj1460247

Cited by 142 publications

(39 citation statements)

References 27 publications

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“…12 -14) Mouse splenocytes were induced to blastogenesis by SBA by the treatment with neuraminidase. 12,13) In our results, the ConA-induced proliferation was affected by neuraminidase treatment. However neither neuraminidase-treated nor non-treated splenocytes were affected by their culture with SP-MAFI (Fig.…”

Section: Biological Activity Of Sp-mafi In Vitrosupporting

confidence: 48%

Isolation and Characterization of a Novel Immunomodulating Fraction from Soybeans

Koga

Kikuchi

1993

Bioscience, Biotechnology, and Biochemistry

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Section: Biological Activity Of Sp-mafi In Vitrosupporting

confidence: 48%

Isolation and Characterization of a Novel Immunomodulating Fraction from Soybeans

Koga

Kikuchi

1993

Bioscience, Biotechnology, and Biochemistry

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“…There is also preliminary evidence which might indicate such a Ca2+ requirement in thyroidstimulating-hormone-treated thyroid (Zor et al, 1968), although further work is needed on this system. Second, the effects of compound A23187 on 32p incorporation into phosphatidylinositol, although significant, do not appear to be dependent on the presence of extracellular Ca2 , whereas the triggering of the K+ efflux from parotid fragments with the same concentration of this agent does depend on a supply of extracellular Ca2+ (Selinger et al, 1974 Maino et al, 1975), to test the generality of this conclusion. The results obtained have, however, not provided conclusive evidence either for or against a role for Ca2+ in the phosphatidylinositol response of lymphocytes, despite the fact that phosphatidylinositol breakdown in a soluble fraction from lymphocytes has a requirement for Ca2+ (Allan & Michell, 1974b).…”

Section: Discussionmentioning

confidence: 99%

The relationship of calcium to receptor-controlled stimulation of phosphatidylinositol turnover. Effects of acetylcholine, adrenaline, calcium ions, cinchocaine and a bivalent cation ionophore on rat parotid-gland fragments

Jones¹,

Michell²

1975

Biochemical Journal

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1. The possibility that Ca2+ ions are involved in the control of the increased phosphatidylinositol turnover which is provoked by a-adrenergic or muscarinic cholinergic stimulation of rat parotid-gland fragments has been investigated. Both types of stimulation provoked phosphatidylinositol breakdown, which was detected either chemically or radiochemically, and provoked a compensatory synthesis of the lipid, detected as an increased rate of incorporation of 32p, into phosphatidylinositol. 2. Acetylcholine had little effect on the incorporation of labelled glycerol, whereas adrenaline stimulated it significantly, but to a much lower extent than 32p incorporation: this suggests that the response to acetylcholine was entirely accounted for by renewal of the phosphorylinositol head-group of the lipid, but that some synthesis de novo was involved in the response to adrenaline. 3. The responses to both types ofstimulation, whether measured as phosphatidylinositol breakdown or as phosphatidylinositol labelling, occurred equally well in incubation media containing 2.5 mM-Ca2+ or 0.2mM-EGTA [ethanedioxybis(ethylamine)-tetra-acetic acid]. 4. Incubation with a bivalent cation ionophore (A23187) led to a small and more variable increase in phosphatidylinositol labelling with 32PI, which occurred whether or not Ca2+ was available in the extracellular medium: this was not accompanied by significant phosphatidylinositol breakdown. 5. Cinchocaine, a local anaesthetic, produced parallel increases in the incorporation of Pi and glycerol into phosphatidylinositol. This is compatible with its known ability to inhibit phosphatidate phosphohydrolase (EC 3.1.3.4) and increase phosphatidylinositol synthesis de novo in other cells. 6. These results indicate that the phosphatidylinositol turnover evoked by a-adrenergic or muscarinic cholinergic stimuli in rat parotid gland probably does not depend on an influx of Ca2+ into the cells in response to stimulation. This is in marked contrast with the Ks efflux from this tissue, which is controlled by the same receptors, but is strictly dependent on the presence of extracellular Ca2+. The Ca2+-independence of stimulated phosphatidylinositol metabolism may mean that it is controlled through a mode ofreceptor function different from that which controls other cell responses. Alternatively, it can be interpreted as indicating that stimulated phosphatidylinositol breakdown is intitnately involved in the mechanisms of action of a-adrenergic and muscarinic cholinergic receptor systems.The increased phosphatidylinositol turnover which occurs in many tissues when exposed to appropriate extracellular stimuli is probably a result of an increase in the rate ofremoval ofthe phosphorylinositol group of the lipid (see Michell (1975) for review]. In support of this view, it has been demonstrated that acetylcholine and pancreozymin cause a decrease in the phosphatidylinositol content of mouse pancreas (Hokin-Neaverson, 1974a,b) and that acetylcholine has the same effect on rat parotid-gland fragments . In the ...

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“…[14] and is expressed as a ratio of the migration of nucleoids from unstimulated cells (mean f SEM of 5 separate experiments). The arrow indicates the migration rate of nucleoids from CEM lymphoblastoid cells Soon after the binding of mitogen an increase in the breakdown and resynthesis of inositol lipids can be detected in the plasma membrane [21]. This was followed by the incorporation of [3H]inositol or inorganic [32P]phosphate into lipids.…”

Section: Early Events In Lymphocyte Activationmentioning

confidence: 99%

“…Similarly, the early PHA-stimulated turnover of plasma membrane inositol phospholipids was not affected by inhibitors of ADPRT (Table 1). These studies place the site of action of inhibitors after the binding of mitogen to the cell surface and some subsequent plasma membrane events (possibly involved in transmission of the stimulatory signal to the cell's interior [21,35]) but before the rejoining of DNA breaks. These changes in DNA may be directly involved in controlling the expression of genes which cause the subsequent synthesis of RNA and protein and eventually cell proliferation and expression of effector functions.…”

Section: Discussionmentioning

confidence: 99%

“…The PHA-stimulated turnover of phosphatidylinositol and phosphatidylinositol phosphates [21] was measured after preincubating lymphocytes at a concentration of 2 x 107/ml for 1 h at 37 "C in the presence of either phosphate-free minimal essential medium (Gibco). suppleomented with non-essential amino acids, 2 mM glutamine, 10/u dialysed fetal calf serum and 20 -50 pCiiml inorganic (32P)phosphate (carrier-free; Amersham) or medium 199 (Gibco) supplemented with 2 mM glutamine, 10% dialysed fetal calf serum and 5 -10 pCi/ml rny0-[2-~H]inositol (1 0 Ci/mmol ; Amersham).…”

Section: Turnover Of' Inositol Phospholipidsmentioning

confidence: 99%

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Rejoining of DNA strand breaks is an early nuclear event during the stimulation of quiescent lymphocytes

Johnstone

1984

Eur J Biochem

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Activation of quiescent human peripheral blood lymphocytes or purified T cells by the mitogen, phytohemagglutinin (PHA), involves a rapid rejoining of DNA breaks present in the resting cells as detected by both nucleoid sedimentation analysis and rate of strand unwinding in alkali. Inhibitors of the enzyme ADP-ribosyltransferase (ADPRT) prevent activation of peripheral lymphocytes or T cells by PHA or concanavalin A in a dose-dependent manner, but only if present during the early stages. They do not affect subsequent proliferation if added later, nor do they inhibit the growth of lymphoblastoid cell lines. The inhibitors slow the rejoining of DNA breaks but do not affect the binding of mitogen to the cell surface or the early PHA-stimulated turnover of plasma membrane inositol phospholipids. DNA breaking and rejoining, regulated by ADPRT, may be involved in controlling gene expression during differentiation.Cell differentiation is the process by which genetic information is selectively expressed to produce cells with various morphologies and functions. This process is fundamentally important not only in the development of multicellular organisms but also in the life cycles of many single-celled eukaryotes. It has been known for some time that different types of differentiated cells contain different populations of messenger RNA, which are translated to produce the proteins peculiar to each type. However, many of the processes involved in the integrated changes, necessary for selectively expressing genetic information during differentiation, are still obscure.From work on chick embryo muscle cells the transient appearance of single-strand breaks in DNA, regulated by nuclear ADP-ribosyltransferase (ADPRT), has been proposed as part of a general mechanism for eukaryotic differentiation [l, 21. ADPRT is a DNA-dependent enzyme, which covalently attaches ADP-ribose moieties, derived from NAD, to many proteins [3,4]. Breaks in DNA strongly stimulate ADPRT [5,6] and it has been proposed that the enzyme regulates DNA repair [7,8] by increasing the activity of DNA ligase I1 [9,10].The stimulation of quiescent lymphocytes in vitro to change their morphology, proliferate and acquire effector functions has been widely studied at the molecular level [l I -141 because of its relevance to the immune system and also as a model for cell differentiation in general. This paper supports the hypothesis of Farzaneh et al. [1,2] by demonstrating the rejoining of DNA breaks soon after mitogen stimulation of human peripheral blood lymphocytes using two independent assays. Furthermore, the process of lymphocyte activation is blocked by competitive inhibitors of ADPRT. The relationship of DNA break rejoining and ADPRT activity to each other and to other molecular events in lymphocyte activation is investigated and the study also extended to purified T lymphocytes and lymphoblastoid cell lines to simplify interpretation of the data. A preliminary report of one aspect of this work has been published [15]. MATERIALS AND METHODS CellsPeripher...

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Relationship between enhanced turnover of phosphatidylinositol and lymphocyte activation by mitogens

Cited by 142 publications

References 27 publications

Isolation and Characterization of a Novel Immunomodulating Fraction from Soybeans

Isolation and Characterization of a Novel Immunomodulating Fraction from Soybeans

The relationship of calcium to receptor-controlled stimulation of phosphatidylinositol turnover. Effects of acetylcholine, adrenaline, calcium ions, cinchocaine and a bivalent cation ionophore on rat parotid-gland fragments

Rejoining of DNA strand breaks is an early nuclear event during the stimulation of quiescent lymphocytes

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