A delayed and sustained rise of cytosolic calcium is elicited by oxidized LDL in cultured bovine aortic endothelial cells

Nègre‐Salvayre, Anne; Fitoussi, Guylène; Réaud, Valerie; Pieraggi, M T; Thiers, Jean-Claude; Salvayre, Robert

doi:10.1016/0014-5793(92)80101-l

Cited by 59 publications

(27 citation statements)

References 45 publications

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“…However, in contrast to growth factors, moxLDL is a nonspecific mediator that triggers a broad spectrum of cellular signals. [5][6][7][8][9][10][11] For instance, moxLDL-induced PDGFR␤ activation is similar to that of EGFR, 12 thus extending the concept that moxLDL activates various tyrosine kinase receptors and suggesting that besides their classic role of transducers of growth factors signaling, PDGFR␤ and EGFR may act as cellular sensors for oxidative stress and oxidized lipids.…”

Section: Discussionmentioning

confidence: 99%

“…3,4 Oxidized LDL (oxLDL) is present in atherosclerotic areas 3 and elicits changes in (1) lipoprotein metabolism (foam cells), (2) gene expression (adhesion molecules, cytokines, growth factors, coagulation proteins), (3) cell migration, motility, and contractility, (4) cell proliferation; (5) cell viability/death, and (6) local immune response. 3 OxLDL triggers or alters various signaling pathways, 5 namely calcium, 6 trimeric G proteins and cAMP, 7 phospholipase D, 8 ceramide, 9 PPAR␥, 10 and epidermal growth factor receptor (EGFR activation being associated with 4-hydroxynonenal [4-HNE] derivatization). 11 We have examined whether this concept may be extended to platelet-derived growth factor receptor ␤ (PDGFR␤), a tyrosine kinase receptor of importance in atherogenesis.…”

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Mildly Oxidized LDL Induces Activation of Platelet-Derived Growth Factor β-Receptor Pathway

et al. 2001

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Background-Mildly oxidized LDL (moxLDL) is thought to play a role in atherogenesis. MoxLDL induces derivatization of cell proteins and triggers a variety of intracellular signaling. We aimed to investigate whether moxLDL-induced protein derivatization may influence the activity of platelet-derived growth factor receptor ␤ (PDGFR␤), a tyrosine kinase receptor of major importance in vascular biology and atherogenesis. Methods and Results-In cultured rabbit arterial smooth muscle cells, moxLDL induces activation of the PDGFR␤ signaling pathway, as shown by PDGFR␤ tyrosine phosphorylation on Western blot and coimmunoprecipitation of SH2-containing proteins. The cellular events involved in the moxLDL-induced PDGFR␤ activation can be summarized as follows. Oxidized lipids from moxLDL trigger two phases of PDGFR␤ activation involving two separate mechanisms, as shown by experiments on cultured cells (in situ) and on immunopurified PDGFR␤ (in vitro): (1) the first phase may be mediated by 4-hydroxynonenal, which induces PDGFR␤ adduct formation and subsequent PDGFR␤ activation (antioxidant-insensitive step); (2) the second phase involves ceramide-mediated generation of H 2 O 2 (these steps being inhibited by tosylphenylalanylchloromethylketone, an inhibitor of ceramide formation, and by antioxidant BHT, exogenous catalase, or overexpressed human catalase). Because 4-hydroxynonenal-PDGFR␤ adducts are also detected in atherosclerotic aortas, it is suggested that this novel mechanism of moxLDL-induced PDGFR␤ activation may occur during atherogenesis. Conclusions-MoxLDL acts as a local autoparacrine mediator in the vascular wall, and PDGFR␤ acts as a sensor for both oxidized lipids and oxidative stress. This constitutes a novel mechanism of PDGFR␤ activation in atherosclerotic areas.

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Mildly Oxidized LDL Induces Activation of Platelet-Derived Growth Factor β-Receptor Pathway

et al. 2001

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“…1 Oxidized LDL (oxLDL) is taken up by macrophages via the scavenger receptors, 2 promoting foam cell formation and fatty plaque development. OxLDL acquires molecular epitopes that are cytotoxic for endothelial cells, 3 stimulate chemotaxis and recruitment of monocytes, 4 and induce macrophage proliferation. 5 In addition, oxLDL is antigenic.…”

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Antibodies Against Oxidized LDL and Carotid Artery Intima-Media Thickness in a Healthy Population

Fukumoto

Shoji

Emoto

et al. 2000

ATVB

125

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Abstract-Oxidation of LDLs plays an important role in atherosclerosis, and immune response to oxidized LDL (oxLDL) may modulate atherogenesis. Although immunization with oxLDL is shown to suppress atherogenesis in animal models, the role of the immune response to oxLDL is not well established in humans. We investigated the relationship between the titer of anti-oxLDL antibody (oxLDL Ab) and arterial wall thickness in a healthy population with no clinical signs of atherosclerosis. Intima-media thickness of the carotid arteries (CA-IMT) was measured by high-resolution B-mode ultrasonography in 446 healthy subjects. The titer of IgG-class oxLDL Ab was measured by a solid-phase ELISA. In univariate analysis, CA-IMT correlated positively with age, systolic blood pressure, total cholesterol, triglyceride, LDL cholesterol, body mass index, and waist-to-hip ratio, whereas it correlated negatively with HDL cholesterol and oxLDL Ab titer. The inverse association between oxLDL Ab titer and CA-IMT remained significant in multiple regression analysis, which took other confounding variables into account. These results indicate an independent inverse relationship between oxLDL Ab titer and CA-IMT in healthy subjects, supporting the hypothesis that immune response to oxLDL may have a protective role at an early stage of human atherosclerosis.

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“…Taken together with our previous findings, the results suggest that Ca 2ϩ may play a role in regulation of homologous recombination in vivo. This role of Ca 2ϩ seems especially compelling because (i) Ca 2ϩ is known as a common intracellular regulator (24), and (ii) Ca 2ϩ concentration rises in response to DNA damage (25)(26)(27)(28)(29)(30) and during meiosis (31), at the time when homologous recombination occurs. We also found that the mechanism of Ca 2ϩ -dependent stimulation of the DNA strand exchange activity of hDmc1 protein differs significantly from that of hRad51 protein, in which inhibition of the ATPase activity plays the primary role.…”

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Activation of Human Meiosis-specific Recombinase Dmc1 by Ca2+

Bugreev

Golub

Stasiak

et al. 2005

Journal of Biological Chemistry

104

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Rad51 and its meiotic homologIn most eukaryotic organisms, meiotic recombination is required for generation of genetic diversity and for accurate segregation of homologous chromosomes (1-3). Mutations that impair meiotic recombination have been reported to increase non-disjunction in Schizosaccharomyces pombe, Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila, mice, and humans; malfunction of meiotic recombination is a leading cause of trisomies in humans (4).The molecular mechanisms of meiotic recombination have been extensively studied, especially in yeast. Meiotic recombination is initiated by DNA double strand breaks introduced in specific regions of chromosomes by a specialized enzyme, Spo11 (5, 6). Consequently, the mechanism of meiotic recombination appears to be closely related to the process of double strand break repair (7-10). The double-stranded DNA (dsDNA) 1 ends are resected to produce an intermediate with a 3Ј-overhanging single-stranded DNA (ssDNA) tail in a process that involves the Mre11/Rad50/Xrs2 heterotrimer (11). The consequent steps of meiotic recombination require Rad51 and Dmc1 proteins and other members of the Rad52 epistasis group (12). It is known that both Rad51 and Dmc1 can polymerize on the ssDNA tails to form extended nucleoprotein complexes that promote a search for homologous DNA and that perform DNA strand exchange (13-17). Rad51 and Dmc1 proteins have significant structural homology, sharing 52% identical amino acid residues, and display similar biochemical properties. However, these proteins may play distinct roles in vivo. Although Rad51 protein is expressed in both mitotic and meiotic cells, Dmc1 is a meiosis-specific protein. In mammals, Rad51 is an essential protein; RAD51 Ϫ/Ϫ knockouts in the mouse cause embryonic lethality. In contrast, DMC1 Ϫ/Ϫ knockouts are viable, but sterile (18,19).In vitro, under standard conditions in the presence of ATP and Mg 2ϩ , human (h) Dmc1 protein forms a peculiar structure on ssDNA defined as stacks of octameric rings (20) and weakly promotes DNA strand exchange (15, 21). Recently, it was found that KCl at elevated concentrations (100 -200 mM) strongly stimulates the DNA strand exchange activity of hDmc1 protein and also promotes the formation of hDmc1⅐ssDNA helical nucleoprotein filaments (17).Previously, we demonstrated that Ca 2ϩ activates the DNA strand exchange activity of hRad51 protein (22) and that Ca 2ϩ is required for stimulation of hRad51 protein by hRad54 protein (23). Here, we examine the effect of Ca 2ϩ on the DNA strand exchange activity of hDmc1. The results show that the DNA strand exchange activity of hDmc1 protein is greatly enhanced by Ca 2ϩ . Taken together with our previous findings, the results suggest that Ca 2ϩ may play a role in regulation of homologous recombination in vivo. This role of Ca 2ϩ seems especially compelling because (i) Ca 2ϩ is known as a common intracellular regulator (24), and (ii) Ca 2ϩ concentration rises in response to DNA damage (25-30) and during meiosis (31), at the time when ho...

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A delayed and sustained rise of cytosolic calcium is elicited by oxidized LDL in cultured bovine aortic endothelial cells

Cited by 59 publications

References 45 publications

Mildly Oxidized LDL Induces Activation of Platelet-Derived Growth Factor β-Receptor Pathway

Mildly Oxidized LDL Induces Activation of Platelet-Derived Growth Factor β-Receptor Pathway

Antibodies Against Oxidized LDL and Carotid Artery Intima-Media Thickness in a Healthy Population

Activation of Human Meiosis-specific Recombinase Dmc1 by Ca2+

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