Curvature stress and polymorphism in membranes

Janes, Nathan

doi:10.1016/0009-3084(96)02578-9

Cited by 39 publications

(38 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this context, numerous reports show that the nonlamellar phases, or the propensity to form them, increase the binding to membranes and activity of PKC (Dawson et al, 1984;Epand et al, 1991;Escribá et al, 1995;Giorgione et al, 1995;Mosior et al, 1996;Goñ i and Alonso, 1999). In fact, diacylglycerols activate PKC not only by a direct binding to the Cys-rich C1 domain of the enzyme but also by inducing hexagonal (H II ) phases or increasing the nonlamellar phase propensity of membranes (Dawson et al, 1984;Epand, 1985;Epand and Bottega, 1988;Epand and Lester, 1990;Goldberg et al, 1994;Janes, 1996). In a similar manner, Minerval and structural analogs are able to lower the temperature of the lamellar-to-hexagonal (H II ) phase transition of model membranes.…”

Section: Resultsmentioning

confidence: 98%

Membrane Structure Modulation, Protein Kinase Cα Activation, and Anticancer Activity of Minerval

Martínez¹,

Vögler²,

Casas³

et al. 2005

Molecular Pharmacology

View full text Add to dashboard Cite

Most drugs currently used for human therapy interact with proteins, altering their activity to modulate the pathological cell physiology. In contrast, 2-hydroxy-9-cis-octadecenoic acid (Minerval) was designed to modify the lipid organization of the membrane. Its structure was deduced following the guidelines of the mechanism of action previously proposed by us for certain antitumor drugs. The antiproliferative activity of Minerval supports the above-mentioned hypothesis. This molecule augments the propensity of membrane lipids to organize into nonlamellar (hexagonal H II ) phases, promoting the subsequent recruitment of protein kinase C (PKC) to the cell membrane. The binding of the enzyme to membranes was marked and significantly elevated by Minerval in model (liposomes) and cell (A549) membranes and in heart membranes from animals treated with this drug. In addition, Minerval induced increased PKC␣ expression (mRNA and protein levels) in A549 cells. This drug also induced PKC activation, which led to a p53-independent increase in p21 CIP expression, followed by a decrease in the cellular concentrations of cyclins A, B, and D3 and cdk2. These molecular changes impaired the cell cycle progression of A549 cells. At the cellular and physiological level, administration of Minerval inhibited the growth of cancer cells and exerted antitumor effects in animal models of cancer without apparent histological toxicity. The present results support the potential use of Minerval and related compounds in the treatment of tumor pathologies.

show abstract

Section: Resultsmentioning

confidence: 98%

Membrane Structure Modulation, Protein Kinase Cα Activation, and Anticancer Activity of Minerval

Martínez¹,

Vögler²,

Casas³

et al. 2005

Molecular Pharmacology

View full text Add to dashboard Cite

show abstract

“…Pure-PC liposomes released ϳ40% of their aqueous contents in 30 min, but when PC-PE (2:1 molar ratio) liposomes were used, 80% efflux was observed. PE is well known for its ability to induce negative curvature and eventually form non-bilayer (mostly hexagonal II) phases (13,25). The effect of PE was compensated by lyso PC, a lipid whose geometry is the opposite of that of PE (22).…”

Section: Resultsmentioning

confidence: 99%

“…Ch facilitates the lamellar-to-nonlamellar transition (10,25) and increases the molecular order of the phospholipid acyl chains (23), among other properties. In our system, Ch greatly enhanced the rate of ACT-induced liposomal efflux in a dose-dependent manner, and the effect became significant above 20 mol% in PC bilayers (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Scott and Zakim (35) observed that Ch lowered the energy barrier for insertion of integral membrane proteins into bilayers. Ch certainly favors the formation of nonlamellar structures (10,25); it also has a number of other effects on the physical properties of the bilayer. The ability of Ch to increase the static order of phospholipid hydrocarbon chains may be relevant in this context.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Membrane Restructuring by Bordetella pertussis Adenylate Cyclase Toxin, a Member of the RTX Toxin Family

et al. 2004

View full text Add to dashboard Cite

Adenylate cyclase toxin (ACT) is secreted by Bordetella pertussis, the bacterium causing whooping cough. ACT is a member of the RTX (repeats in toxin) family of toxins, and like other members in the family, it may bind cell membranes and cause disruption of the permeability barrier, leading to efflux of cell contents. The present paper summarizes studies performed on cell and model membranes with the aim of understanding the mechanism of toxin insertion and membrane restructuring leading to release of contents. ACT does not necessarily require a protein receptor to bind the membrane bilayer, and this may explain its broad range of host cell types. Adenylate cyclase toxin (ACT) is secreted by Bordetella pertussis, the bacterium responsible for whooping cough. The 1,706-residue protein can enter eukaryotic cells, where, upon activation by endogenous calmodulin, it increases the intracellular levels of cyclic AMP, leading to severe alterations in cellular physiology, often referred to as intoxication (see reference 28 for a review). ACT belongs to the so-called RTX (repeats in toxin) family of proteins, characterized by a Ca 2ϩ -binding nonapeptide repeated in tandem several times, up to 30 to 38 repeats in the case of ACT, depending on the stringency of repeat definition. This toxin represents the most evolutionarily divergent example of the family (for reviews of RTX proteins, see references 40 and 41). Unlike most other members of the family, ACT remains associated with the bacterial surface after secretion, apparently associated with filamentous hemagglutinin (42).In common with other members of the RTX family, and apart from its unique adenylate cyclase activity, ACT has a capacity to induce cell lysis, usually demonstrated as hemolysis. ACT-induced hemolysis requires higher toxin concentrations (by more than 1 order of magnitude) and occurs more slowly than intoxication (17). Active ACT is acylated at two positions inside the chain, and the acylation pattern appears to affect hemolysis, rather than intoxication (19). Moreover, dose-response experiments suggest that intoxication can be triggered by ACT monomers, while hemolysis is a more cooperative event, mediated by at least trimers (5, 17, 32). These and other observations have led to the conclusion that hemolysis and intoxication occur through separate mechanisms (17,28,32,34).Unlike intoxication, ACT-induced cell lysis has received relatively little attention. Benz et al. (4) and Szabo et al. (39), using planar lipid bilayers, demonstrated that ACT increased membrane conductance, giving rise to small, transient, cationselective channels. These authors also found that ACT was less active in this respect than ␣-hemolysin (HlyA), another member of the RTX family, secreted by Escherichia coli (4). In general, the mechanism of HlyA-induced hemolysis has been studied in more detail (see references 16 and 40 for reviews). In particular, studies in one of our laboratories have examined the capacity of HlyA to destroy the permeability barrier of pure-lipid vesicl...

show abstract

“…PC tends to form bilayers with little curvature, while PE imposes a negative curvature on these lipid bilayers (Janes, 1996). Conversely, introduction of the micelle-forming LPC into a PC membrane results in a positive curvature.…”

Section: The Lipid Peroxidation Process Generates Oxidized Phospholipidsmentioning

confidence: 98%

Lipid peroxidation of membrane phospholipids generates hydroxy-alkenals and oxidized phospholipids active in physiological and/or pathological conditions

Catalá

2009

Chemistry and Physics of Lipids

640

437

View full text Add to dashboard Cite

Curvature stress and polymorphism in membranes

Cited by 39 publications

References 68 publications

Membrane Structure Modulation, Protein Kinase Cα Activation, and Anticancer Activity of Minerval

Membrane Structure Modulation, Protein Kinase Cα Activation, and Anticancer Activity of Minerval

Membrane Restructuring by Bordetella pertussis Adenylate Cyclase Toxin, a Member of the RTX Toxin Family

Lipid peroxidation of membrane phospholipids generates hydroxy-alkenals and oxidized phospholipids active in physiological and/or pathological conditions

Contact Info

Product

Resources

About