Divalent cations and chlorpromazine can induce non-bilayer structures in phosphatidic acid-containing model membranes

Verkleij, A.J.; Maagd, Ruud A. de; Leunissen‐Bijvelt, J.; Kruijff, Ben de

doi:10.1016/0005-2736(82)90014-1

Cited by 143 publications

(79 citation statements)

References 25 publications

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“…These drugs have a molecular conic shape with a nonpolar head and a cationic vertex, which induce the formation of non-bilayer arrangements by H H H -preferring lipids, as demonstrated in this work and in others for chlorpromazine [17]. The absence of NPA on smooth rigid liposomes treated either with barium or procainamide cations can be attributed to the high content of saturated fatty acids in their phospholipids, which diminished the fluidity required for lipid mobility during NPA formation.…”

Section: Discussionsupporting

confidence: 67%

Antibodies to non‐bilayer phospholipid arrangements induce a murine autoimmune disease resembling human lupus

et al. 2004

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Antibodies recognizing non-bilayer phospholipid arrangements (NPA) in membrane models and in cell membranes in vivo, triggered an autoimmune-like disease in mice. This exhibited features similar to human lupus and was induced by injecting mice either with the H308 monoclonal antibody specific to NPA, with sera from mice which already had developed the autoimmune disease, or with liposomes treated with the NPA inductors chlorpromazine or procainamide; or with these NPA inductors alone. All these procedures revealed the involvement of antibodies to non-bilayer phospholipids in inducing this autoimmune-like disease. Unraveling the mechanisms of these antibodies might contribute to a better understanding of the molecular and immunological basis of autoimmune diseases like lupus and, hopefully, towards the development of better therapeutic strategies.

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Section: Discussionsupporting

confidence: 67%

Antibodies to non‐bilayer phospholipid arrangements induce a murine autoimmune disease resembling human lupus

et al. 2004

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“…The aim of the current study was to directly measure the spontaneous curvature (the inverse of the spontaneous radius of curvature) of PA and LPA at a physiological pH and salt concentration. Our study extends previous more qualitative studies on the molecular shape of (L)PA (21)(22)(23)(24), and now allows theoretical models of biomembrane fission to be developed (3,16). We show that, under physiological conditions of pH and ionic strength, PA has a negative spontaneous curvature that is slightly less pronounced than that of dioleoylphosphatidylethanolamine (DOPE), while LPA has a spontaneous curvature that is considerably more positive than that of lysophosphatidylcholine (LPC).…”

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confidence: 77%

Spontaneous Curvature of Phosphatidic Acid and Lysophosphatidic Acid

et al. 2005

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The formation of phosphatidic acid (PA) from lysophosphatidic acid (LPA), diacylglycerol, or phosphatidylcholine plays a key role in the regulation of intracellular membrane fission events, but the underlying molecular mechanism has not been resolved. A likely possibility is that PA affects local membrane curvature facilitating membrane bending and fission. To examine this possibility, we determined the spontaneous radius of curvature (R 0p ) of PA and LPA, carrying oleoyl fatty acids, using well-established X-ray diffraction methods. We found that, under physiological conditions of pH and salt concentration (pH 7.0, 150 mM NaCl), the R 0p values of PA and LPA were -46 Å and +20 Å, respectively. Thus PA has considerable negative spontaneous curvature while LPA has the most positive spontaneous curvature of any membrane lipid measured to date. The further addition of Ca 2+ did not significantly affect lipid spontaneous curvature; however, omitting NaCl from the hydration buffer greatly reduced the spontaneous curvature of PA, turning it into a cylindrically shaped lipid molecule (R 0p of -1.3 × 10 2 Å). Our quantitative data on the spontaneous radius of curvature of PA and LPA at a physiological pH and salt concentration will be instrumental in developing future models of biomembrane fission.

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“…Because PA has a tendency to form hexagonal II phase in the presence of Ca 2ϩ (Verkleij et al, 1982) that may lead to membrane destabilization, we additionally tested unsaturated phosphatidylethanolamine with a similar propensity to destabilize membranes (Cullis and de Kruijff, 1979), along with detergents, other phospholipids, and PA metabolic products. The cell death response was detected only in PA-treated leaves, implying that the observed cell death is not due to membrane destabilization or a general effect of phospholipids or their metabolites, but is a specific response to PA itself (Fig.…”

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confidence: 99%

Phosphatidic Acid Induces Leaf Cell Death in Arabidopsis by Activating the Rho-Related Small G Protein GTPase-Mediated Pathway of Reactive Oxygen Species Generation

Gu²,

et al. 2004

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Phosphatidic acid (PA) level increases during various stress conditions. However, the physiological roles of this lipid in stress response remain largely unknown. In this study, we report that PA induced leaf cell death and elevated the levels of reactive oxygen species (ROS) in the whole leaf and single cells. To further elucidate the mechanism of PA-induced cell death, we then examined whether Rho-related small G protein (ROP) 2, which enhanced ROS production in an in vitro assay, is involved in PA-induced ROS production and cell death. In response to PA, transgenic leaves of Arabidopsis expressing a constitutively active rop2 mutant exhibited earlier cell death and higher levels of ROS than wild type (WT), whereas those expressing a dominant-negative rop2 mutant exhibited later cell death and lower ROS. However, in the absence of exogenous PA, no spontaneous cell death or elevated ROS was observed in constitutively active rop2 plants, suggesting that the activation of ROP GTPase alone is insufficient to activate the ROP-mediated ROS generation pathway. These results suggest that PA modulates an additional factor required for the active ROP-mediated ROS generation pathway. Therefore, PA may be an important regulator of ROP-regulated ROS generation and the cell death process during various stress and defense responses of plants.Phosphatidic acid (PA) is implicated in numerous stress responses of plants. Intracellular PA levels increase under various biotic and abiotic stress conditions, including pathogen elicitation (Young et al., 1996;van der Luit et al., 2000), wounding Wang, 1996, 1998; Lee et al., 1997), freezing (Welti et al., 2002), hyperosmotic stress (Munnik et al., 2000), and water deficit (Frank et al., 2000;Munnik et al., 2000). It is suggested that PA is a second messenger in a broad range of stress-signaling pathways in plants and mediates important responses to stresses (Munnik, 2001).PA has many regulatory functions in animal cells, including the regulation of reactive oxygen species (ROS) generation, protein kinase, phosphatase, lipid kinase, phospholipases, intracellular Ca 2ϩ levels, vesicle trafficking, cell proliferation, and cytoskeletal rearrangement (Liscovitch et al., 2000). This lipid also regulates a wide range of important cellular processes in plants, including regulation of ROS generation (Sang et al., 2001a), MAPK activity (Lee et al., 2001), K ϩ channels (Jacob et al., 1999), and actin organization (Lee et al., 2003). Therefore, PA is likely to be involved in numerous physiological processes in plants, including stomatal movement (Jacob et al., 1999), leaf senescence (Fan et al., 1997), various stress responses, and hormone signaling (for review, see Munnik, 2001). In vivo roles of PA in leaf senescence and stomatal closing movement were demonstrated using PLD␣ antisense plants; this mutant plant is delayed in ABA-and ethylene-induced senescence (Ryu and Wang, 1995; Fan et al., 1997;Zien et al., 2001) and in ABA-induced stomatal closing movement (Sang et al., 2001b).A potentia...

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Divalent cations and chlorpromazine can induce non-bilayer structures in phosphatidic acid-containing model membranes

Cited by 143 publications

References 25 publications

Antibodies to non‐bilayer phospholipid arrangements induce a murine autoimmune disease resembling human lupus

Antibodies to non‐bilayer phospholipid arrangements induce a murine autoimmune disease resembling human lupus

Spontaneous Curvature of Phosphatidic Acid and Lysophosphatidic Acid

Phosphatidic Acid Induces Leaf Cell Death in Arabidopsis by Activating the Rho-Related Small G Protein GTPase-Mediated Pathway of Reactive Oxygen Species Generation

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