Diacylglycerol metabolism in SM-3 smooth muscle cells

Migas, Iris; Chuang, Mariette; Sasaki, Yasuo; Severson, David L.

doi:10.1139/y97-158

Cited by 9 publications

(3 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5b). A similar fate has been reported for a variety of other DG molecular species when added to cells, including those with a fatty acid composition identical to that generated by phosphoinositide hydrolysis (Migas et al, 1997). Thus we conclude that the DG produced as a result of hormonal stimulation is channeled to the DG kinase, as previously suggested (Redman et al, 1995).…”

Section: Discussionsupporting

confidence: 70%

Analysis of hormone‐stimulated phosphatidylinositol synthesis

Monaco

Moldover

Walden

2002

Journal Cellular Physiology

View full text Add to dashboard Cite

Agonist-stimulated phosphoinositide turnover is accompanied by compensatory resynthesis of these lipids. Several lines of evidence suggest that resynthesis of phosphatidylinositol (PtdIns) involves phosphorylation of diacylglycerol (DG) (salvage pathway) rather than acylation of glycerol phosphate (de novo pathway), although a contribution from the de novo pathway has not been ruled out. To determine the relative contribution of the de novo and salvage pathways in stimulated PtdIns resynthesis, an inhibitor of de novo synthesis (Triacsin C) was incubated simultaneously with the hormone agonist. Results indicate that at early times (90 min), hormone-stimulated PtdIns synthesis proceeds predominantly via the salvage pathway, although some de novo synthesis is also taking place. At later times (24 h), stimulated synthesis is solely via the de novo pathway. Increasing cellular DG content by either adding exogenous DG or treating cells with bacterial phospholipase C (bPLC) results in deacylation of the DG rather than phosphorylation; however, inhibition of this deacylation fails to stimulate phosphorylation by DG kinase (DGK), suggesting channeling of the DG substrate between PLC and DG kinase. Receptor activation is not required for activation of DGK, since treatment with a calcium ionophore induces the same Triacsin C-insensitive PtdIns synthesis. Depletion of the polyphosphoinositide pools by treatment with wortmannin prevents both hormone and A23187-induced polyphosphoinositide hydrolysis; however, A23187 is still able to induce hydrolysis of PtdIns and subsequent compensatory resynthesis. The inability of R59949 to inhibit either hormone-induced or ionophore-induced PtdIns resynthesis suggests that the alpha isoform is not involved; however, its possible that the channeling phenomenon prevents the inhibitor from gaining access to the diacylglycerol kinase enzyme. Further study will be required to determine which isoform catalyzes hormone-induced resynthesis of PtdIns.

show abstract

Section: Discussionsupporting

confidence: 70%

Analysis of hormone‐stimulated phosphatidylinositol synthesis

Monaco

Moldover

Walden

2002

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…26 -28,50 It was recently demonstrated that bacterial phospholipase C, an enzyme competing with LPL for binding to VSMCs, activates PKC in VSMCs. 51 Our data showing that LPL induces PKC activation in VSMCs and that heat inactivation and PMSF inactivation of the enzyme or heparinase treatment of VSMCs inhibit LPL-induced PKC activation clearly suggest that the enzyme may promote the growth of these cells by stimulating this signaling pathway. The involvement of PKC activation in the direct stimulation of VSMC proliferation by LPL is strengthened by our observations that pharmacological inhibition of PKC by specific PKC inhibitors, including calphostin C and chelerythrin, completely suppresses LPL-induced VSMC proliferation.…”

Section: Discussionmentioning

confidence: 64%

Proliferative Effect of Lipoprotein Lipase on Human Vascular Smooth Muscle Cells

Mamputu

Lévesque

Renier

2000

ATVB

View full text Add to dashboard Cite

Abstract-Vascular smooth muscle cell (VSMC) proliferation is a key event in the development and progression of atherosclerotic lesions. Accumulating evidence suggests that lipoprotein lipase (LPL) produced in the vascular wall may exert proatherogenic effects. The aim of the present study was to examine the effect of LPL on VSMC proliferation. Incubation of growth-arrested human VSMCs with purified endotoxin-free bovine LPL for 48 and 72 hours, in the absence of any added exogenous lipoproteins, resulted in a dose-dependent increase in VSMC growth. Addition of VLDLs to the culture media did not further enhance the LPL effect. Treatment of growth-arrested VSMCs with purified human or murine LPL (1 g/mL) led to a similar increase in cell proliferation. Neutralization of bovine LPL by the monoclonal 5D2 antibody, irreversible inhibition, or heat inactivation of the lipase suppressed the LPL stimulatory effect on VSMC growth. Moreover, preincubation of VSMCs with the specific protein kinase C inhibitors calphostin C and chelerythrine totally abolished LPL-induced VSMC proliferation. In LPL-treated VSMCs, a significant increase in protein kinase C activity was observed. Treatment of VSMCs with heparinase III (1 U/mL) totally inhibited LPL-induced human VSMC proliferation. Taken together, these data indicate that LPL stimulates VSMC proliferation. LPL enzymatic activity, protein kinase C activation, and LPL binding to heparan sulfate proteoglycans expressed on VSMC surfaces are required for this effect. The stimulatory effect of LPL on VSMC proliferation may represent an additional mechanism through which the enzyme contributes to the progression of atherosclerosis. 6 The enzyme is also produced by monocyte-derived macrophages and vascular smooth muscle cells (VSMCs), 2 prominent cellular components of the atherosclerotic lesion. 7-9 Although plasma LPL activity tends to drive lipoprotein metabolism in a nonatherogenic direction, 10 -12 LPL produced in the vascular wall may act as a proatherogenic protein. Indeed, LPL has been shown to mediate uptake of lipoprotein particles by vascular cells, [13][14][15] to promote lipoprotein retention to the extracellular matrix, 16,17 to induce the expression of the proatherogenic cytokine tumor necrosis factor-␣, 18,19 and to enhance monocyte adhesion to endothelial cells. 20,21 Furthermore, recent studies indicate that LPL enhances cellular proteoglycan production 22 and promotes foam cell formation and atherosclerosis in vivo. 23 VSMC migration and proliferation are typical features of intimal hyperplasia and atherogenesis. 24 These biological processes are mediated by cytokines and growth factors released by infiltrating inflammatory cells and neighboring endothelial cells. 25 The proliferative response of VSMCs to various stimuli involves protein kinase C (PKC) activation. 26 -28 In light of our previous study demonstrating that LPL activates PKC in human mononuclear cells, 19 the present study was conducted to investigate whether LPL may exert a direct stimulatory effect ...

show abstract

“…Igal et al stated the possible encryption of intracellular DAGs produced in CHO cell plasma membranes after ingestion by phospholipase C in initiating TAG biosynthesis. Meanwhile, the mechanism of DAG lipase inhibitors added via liposome fusion or via soluble dioctanoyl glycerol remain unclear, particularly on their total inhibitory levels to phospholipase C in NIH 3T3 Swiss fibroblasts. − These results make certain assumptions on the presence of different molecular routes and releasing domains for phospholipase C and perhaps due to metamorphic crystallization happen under different pH conditions and ion strengths. These statements have logical opinions when we are taking into account the molecular labeling of intermediated enzymes and their targeted substrates.…”

Section: Bioavailability Of Glycerols and Glycerolipidsmentioning

confidence: 99%

Newly Structured Lipid-Based Glycerolysis Mechanism: Insights into Glycerolipid Crystal Growth and Function

Saadi,

Nacer,

Ariffin

et al. 2023

ACS Food Sci. Technol.

View full text Add to dashboard Cite

The progressive depletion of chylomicrons and the decomplexation of membrane-promoting factors have a direct link to the ideal levels of glycerolipids. For these reasons, treating thermodynamically balanced molecules like glycerolipids is aimed toward remodulating the physiological function of phospholipidic membranes, limiting the rates of enzymes, and controlling the metaphase assemblies by forming cores like antigens, promoters, effectors, or inhibitors. The abilities of phosphoric ligands for changing the metamorphic properties of glycerols to phosphoglycerols and their crystallinity levels, along with lipoprotein course regimes, have posed significant interest in immune stimulation, structural protection, repair modes, and osmoregulation statuses. This topic is devoted to understanding the roles and functions of glycerolipids in molecular ligand activation, phosphorylation, stability, and interaction. In general, this review is providing insights into glycerolipid prototypes and their mechanization effects in affecting lipid distributions and their crystallization, signaling, and effectiveness.

show abstract

Diacylglycerol metabolism in SM-3 smooth muscle cells

Cited by 9 publications

References 34 publications

Analysis of hormone‐stimulated phosphatidylinositol synthesis

Analysis of hormone‐stimulated phosphatidylinositol synthesis

Proliferative Effect of Lipoprotein Lipase on Human Vascular Smooth Muscle Cells

Newly Structured Lipid-Based Glycerolysis Mechanism: Insights into Glycerolipid Crystal Growth and Function

Contact Info

Product

Resources

About