Effects of lipid constituents on membrane-permeabilizing activity of amphidinols

Morsy, Nagy; Houdai, Toshihiro; Konoki, Keiichi; Matsumori, Nobuaki; Oishi, Tohru; Murata, Michio

doi:10.1016/j.bmc.2007.12.029

Cited by 39 publications

(68 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, maitotoxin does not elicit Ca 2þ influx into artificial phospholipid vesicles (Takahashi et al, 1982;Murata et al, 1992), but does induce Ca 2þ influx into erythrocyte ghosts (Konoki et al, 1999), whose membranes are much more complex. The membrane permeabilizing activity of amphidinols (AM2 and AM3) was remarkably enhanced by the presence of sterols (cholesterol) (Morsy et al, 2008a), or transmembrane protein (glycophorin A) (Morsy et al, 2008b) in artificial liposomes composed of saturated lipids. The possibility that other yet unstudied membrane components serve as the target of lytic compounds cannot be excluded.…”

Section: Discussionmentioning

confidence: 97%

“…Furthermore, several studies on membrane permeation mechanisms of hemolytic and/or lytic polyene-polyhydroxy toxins from dinoflagellates are also reported to relate to membrane sterols. Hemolytic activity of amphidinols isolated from the dinoflagellate Amphidinium klebsii is apparently increased when cholesterol is present in the target membrane (Paul et al, 1996(Paul et al, , 1997Morsy et al, 2008a). Karlotoxins (KmTx) from the dinoflagellate Karlodinium veneficum show different binding affinities to conspecific sterols than to sterols of target species, indicating that the toxin producers may protect themselves by possessing special sterols, e.g.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mode of action of membrane-disruptive lytic compounds from the marine dinoflagellate Alexandrium tamarense

Krock

Tillmann

et al. 2011

Toxicon

View full text Add to dashboard Cite

a b s t r a c tCertain allelochemicals of the marine dinoflagellate Alexandrium tamarense cause lysis of a broad spectrum of target protist cells but the lytic mechanism is poorly defined. We first hypothesized that membrane sterols serve as molecular targets of these lytic compounds, and that differences in sterol composition among donor and target cells may cause insensitivity of Alexandrium and sensitivity of targets to lytic compounds. We investigated Ca 2þ influx after application of lytic fractions to a model cell line PC12 derived from a pheochromocytoma of the rat adrenal medulla to establish how the lytic compounds affect ion flux associated with lysis of target membranes. The lytic compounds increased permeability of the cell membrane for Ca 2þ ions even during blockade of Ca 2þ channels with cadmium. Results of a liposome assay suggested that the lytic compounds did not lyse such target membranes non-specifically by means of detergent-like activity. Analysis of sterol composition of isolates of A. tamarense and of five target protistan species showed that both lytic and non-lytic A. tamarense strains contain cholesterol and dinosterol as major sterols, whereas none of the other tested species contain dinosterol. Adding sterols and phosphatidylcholine to a lysis bioassay with the cryptophyte Rhodomonas salina for evaluation of competitive binding indicated that the lytic compounds possessed apparent high affinity for free sterols and phosphatidylcholine. Lysis of protistan target cells was dose-dependently reduced by adding various sterols or phosphatidylcholine. For three tested sterols, the lytic compounds showed highest affinity towards cholesterol followed by ergosterol and brassicasterol. Cholesterol comprised a higher percentage of total sterols in plasma membrane fractions of A. tamarense than in corresponding whole cell fractions. We conclude therefore that although the molecular targets of the lytic compounds are likely to involve sterol components of membranes, A. tamarense must have a complex selfprotective mechanism that still needs to be addressed.

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Mode of action of membrane-disruptive lytic compounds from the marine dinoflagellate Alexandrium tamarense

Krock

Tillmann

et al. 2011

Toxicon

View full text Add to dashboard Cite

show abstract

“…97 Another possibility lies in the electric dipole interaction between polar functionalities of peptides and ether bonds of LSP. the dinoflagellate Amphidinium species, showed potent antifungal activity, which significantly exceed that of commercial drugs such as amphotericin B. AMs enhance the permeability of the biological membrane in the presence of sterol 104,107 by directly interacting with membrane lipids. Among known antifungal agents, AMs are very unique in lacking nitrogenous functionalities usually present in synthetic drugs, or macrocyclic structures commonly found in polyene-macrolide antibiotics.…”

Section: Activity-relevant Conformation and Bimolecular Interactions mentioning

confidence: 99%

Structural Features of Dinoflagellate Toxins Underlying Biological Activity as Viewed by NMR

Murata

Matsumori

Konoki

et al. 2008

Bulletin of the Chemical Society of Japan

Self Cite

View full text Add to dashboard Cite

Marine dinoflagellates are a rich source of structurally and biologically intriguing secondary metabolites. Among those, maitotoxin may be one of the best known examples, which is the largest natural product known to date and possesses the most potent toxicity known amongst non-proteinaceous compounds. Structural studies of maitotoxin are reviewed with a particular focus on the configuration and mode of action of this unique toxin. In addition, there are many marine natural products which bind to biomembranes to exert their biological activities. To gain a better understanding of their mode of action, conformation, and bimolecular interaction occurring in biomembranes are particularly important. Recent results from NMR studies of membrane systems in the authors' group are reviewed briefly.

show abstract

“…This is similar to the reported mode of action for the structurally similar amphidinols. Several reports have shown that amphidinol 3 (AM3) enhances the permeability of the biological membrane by forming pores or lesions in lipid bilayers, (Houdai et al, 2004, 2005; Morsy et al, 2008; Murata et al, 1999; Oishi et al, 2008; Paul et al 1997) which is thought to be responsible for their potent antifungal activity.…”

Section: Discussionmentioning

confidence: 99%

“…Houdai et al (2005) found evidence for a hairpin structure in amphidinols and that membrane permeabilization was hardly influenced by the bilayer thickness (Morsy et al, 2008). Based on their structural similarities, a hairpin-like structure is also expected for the karlotoxins.…”

Section: Discussionmentioning

confidence: 99%

The cytotoxic mechanism of karlotoxin 2 (KmTx 2) from Karlodinium veneficum (Dinophyceae)

et al. 2015

View full text Add to dashboard Cite

This study demonstrates that the polyketide toxin karlotoxin 2 (KmTx 2) produced by Karlodinium veneficum, a dinoflagellate associated with fish kills in temperate estuaries worldwide, alters vertebrate cell membrane permeability. Microfluorimetric and electrophysiological measurements were used to determine that vertebrate cellular toxicity occurs through non-selective permeabilization of plasma membranes, leading to osmotic cell lysis. Previous studies showed that KmTx 2 is lethal to fish at naturally-occurring concentrations measured during fish kills, while sub-lethal doses severely damage gill epithelia. This study provides a mechanistic explanation for the association between K. veneficum blooms and fish kills that has long been observed in temperate estuaries worldwide.

show abstract

Effects of lipid constituents on membrane-permeabilizing activity of amphidinols

Cited by 39 publications

References 39 publications

Mode of action of membrane-disruptive lytic compounds from the marine dinoflagellate Alexandrium tamarense

Mode of action of membrane-disruptive lytic compounds from the marine dinoflagellate Alexandrium tamarense

Structural Features of Dinoflagellate Toxins Underlying Biological Activity as Viewed by NMR

The cytotoxic mechanism of karlotoxin 2 (KmTx 2) from Karlodinium veneficum (Dinophyceae)

Contact Info

Product

Resources

About