Interaction of Presynaptically Toxic Phospholipases A<sub>2</sub>with Membrane Receptors and Other Binding Sites

Tzeng, Mu-Chin

doi:10.3109/15569549309084185

Cited by 28 publications

(9 citation statements)

References 186 publications

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“…Conversely, CTX proved to be convulsant (Brazil, 1972) despite a relatively low catalytic activity in vitro (Lambeau et al, 1989;Radvanyi et al, 1989). Numerous studies stressed the heterogeneity of the binding sites (Dev et al, 1997;Lambeau et al, 1989; as reviewed by Lambeau et al, 1997 andTzeng, 1993) and a role for central receptors in the neurotoxicity and the lethality has been proposed by various teams (Lambeau et al, 1989;Tzeng et al, 1995). However, their implication in the epileptogenic properties of sPLA 2 s has not really been investigated as yet.…”

Section: Introductionmentioning

confidence: 99%

Secreted phospholipase A2-induced neurotoxicity and epileptic seizures after intracerebral administration: An unexplained heterogeneity as emphasized with paradoxin and crotoxin

et al. 1998

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After intracerebral injection, some toxic secreted phospholipases A2 (sPLA2) can induce epileptic seizures which bases are currently ill known. We undertook the detailed study of the central neurotoxicity of paradoxin (PDX), an analog of taipoxin, in rodents. Since literature strongly suggests a high variability in the sPLA2 epileptogenic properties, we compared, in an acute model, PDX with crotoxin (CTX), known to induce seizures and that may bind to similar neuronal receptors. Related toxic enzymes (ammodytoxin A, ATX A, and CTX subunit CB) and the non neurotoxic sPLA2 from pancreas and PLA2 analog ammodytin L (AML) were also tested. Despite being highly neurotoxic, PDX did not induce either convulsions or long-lasting seizure fits. The results obtained with the other enzymes showed that toxic sPLA2s can effectively be differentiated based on two criteria: the presence of cortically recorded epileptic paroxysmal discharges (E) and convulsions (C). We thus propose to classify the toxic sPLA2s into different groups depending on their epileptogenic properties: E-C-(PDX), E+C+ (CTX, CB), and E-C+ (ATX A). The non toxic AML and pancreatic enzyme were E-C-. Moreover, the results obtained with AML, and preliminarily with chemically inhibited CB, suggested that phospholipid hydrolysis is important to trigger seizures and convulsions. However, PDX and CTX that possess highly different epileptogenic properties exerted comparable, although slightly different, catalytic activities. Similarly, histological evaluations of the brain of PDX and CTX-treated rats (H&E staining, GFAP immunodetection, hsp70 and c-fos mRNA detection) did not provide satisfactory clues to explain these large differences. Further studies are strongly required.

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Section: Introductionmentioning

confidence: 99%

Secreted phospholipase A2-induced neurotoxicity and epileptic seizures after intracerebral administration: An unexplained heterogeneity as emphasized with paradoxin and crotoxin

et al. 1998

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“…Fax: (886) (2) 2363-5038. 1 The sequence data are available from GenBank/EMBL/DDBJ under accession number AJH001929.…”

Section: Methodsmentioning

confidence: 99%

“…Many of them also exhibit neurotoxicity, myotoxicity, coagulation effects and other biological actions, which may or may not be related to hydrolysis of phospholipids. A small number of the PLA 2 proteins, including crotoxin from the South American rattlesnake Crotalus durissus terrificus , affect primarily the presynaptic site to cause ultimate blockade of synaptic transmission by inhibiting the release of neurotransmitters, though most of them also show postsynaptic toxicity and other effects (see [1–12]for recent reviews). Previously we have identified high‐affinity binding proteins for crotoxin by photoaffinity labeling and chemical cross‐linking techniques [13–15].…”

Section: Introductionmentioning

confidence: 99%

Crocalbin: a new calcium‐binding protein that is also a binding protein for crotoxin, a neurotoxic phospholipase A₂

1999

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Utilizing Marathon-ready cDNA library and a genespecific primer corresponding to a partial amino acid sequence determined previously, the complete nucleotide sequence for the cDNA of crocalbin, which binds crotoxin (a phospholipase A 2 ) and Ca 2+ , was obtained by polymerase chain reaction. The open reading frame of the cDNA encodes a novel polypeptide of 315 amino acid residues, including a signal sequence of 19 residues. This protein contains six potential Ca 2+ -binding domains, one Nglycosylation site, and a large amount of acidic amino acid residues. The ability to bind Ca 2+ has been ascertained by calcium overlay experiment. Evidenced by sequence similarity in addition, it is concluded that crocalbin is a new member of the reticulocalbin family of calcium-binding proteins.z 1999 Federation of European Biochemical Societies.

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“…In other words, ATX might act as a homodimeric neurotoxin. It is widely accepted that PLA 2 presynaptic neurotoxins might interact with speci®c acceptors on the presynaptic membranes via the neurotoxic sites at the molecular surface (Tzeng, 1993;Kwong et al, 1995) and several groups have reported the puri®cation and characterization of membrane proteins which might serve as the acceptors for presynaptic neurotoxins (Hseu et al, 1990;Yen & Tzeng, 1991). It has been proposed that the regions around turn 55±61 and stretch 85±91, which show unique local conformation and electrostatic characteristics, might be the neurotoxic site of ATX, i.e.…”

Section: Research Papersmentioning

confidence: 99%

“…A number of secretory PLA 2 presynaptic neurotoxins have been isolated from snake venoms (for reviews, see Yang, 1994;Hawgood & Bon, 1991;Tzeng, 1993; for reviews on PLA 2 , see Arni & Ward, 1996;Mukherjee et al, 1994;Dennis, 1994). Some of them, e.g.…”

Section: Introductionmentioning

confidence: 99%

Structure of agkistrodotoxin in an orthorhombic crystal form with six molecules per asymmetric unit

Tang

Lin

1999

Acta Crystallogr D Biol Cryst

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The structure of agkistrodotoxin crystallized under basic conditions has been determined at 2.8 A resolution by the molecular-replacement technique and refined to a crystallographic R factor of 0.194 and a free R factor of 0.260 with good stereochemistry. The molecular packing in the crystal differs from other PLA(2)s. The six molecules in the asymmetric unit form three dimers linked by Ca(2+) ions in a near-perfect six-ligand octahedral coordinating system. Extensive intermolecular hydrophobic interactions occur at the interfacial recognition site of each neurotoxin molecule, which provides an insight into phospholipase A(2)-membrane interactions. This hydrophobic interaction-induced molecular association along the interfacial recognition site suggests a self-protection mechanism of agkistrodotoxin.

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Interaction of Presynaptically Toxic Phospholipases A₂with Membrane Receptors and Other Binding Sites

Cited by 28 publications

References 186 publications

Secreted phospholipase A2-induced neurotoxicity and epileptic seizures after intracerebral administration: An unexplained heterogeneity as emphasized with paradoxin and crotoxin

Secreted phospholipase A2-induced neurotoxicity and epileptic seizures after intracerebral administration: An unexplained heterogeneity as emphasized with paradoxin and crotoxin

Crocalbin: a new calcium‐binding protein that is also a binding protein for crotoxin, a neurotoxic phospholipase A₂

Structure of agkistrodotoxin in an orthorhombic crystal form with six molecules per asymmetric unit

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Interaction of Presynaptically Toxic Phospholipases A2with Membrane Receptors and Other Binding Sites

Cited by 28 publications

References 186 publications

Secreted phospholipase A2-induced neurotoxicity and epileptic seizures after intracerebral administration: An unexplained heterogeneity as emphasized with paradoxin and crotoxin

Secreted phospholipase A2-induced neurotoxicity and epileptic seizures after intracerebral administration: An unexplained heterogeneity as emphasized with paradoxin and crotoxin

Crocalbin: a new calcium‐binding protein that is also a binding protein for crotoxin, a neurotoxic phospholipase A2

Structure of agkistrodotoxin in an orthorhombic crystal form with six molecules per asymmetric unit

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Product

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Interaction of Presynaptically Toxic Phospholipases A₂with Membrane Receptors and Other Binding Sites

Crocalbin: a new calcium‐binding protein that is also a binding protein for crotoxin, a neurotoxic phospholipase A₂