Document Detail

Snake phospholipase A2 neurotoxins enter neurons, bind specifically to mitochondria, and open their transition pores.
MedLine Citation:
PMID:  18809685     Owner:  NLM     Status:  MEDLINE    
Snake presynaptic neurotoxins with phospholipase A(2) activity are potent inducers of paralysis through inhibition of the neuromuscular junction. These neurotoxins were recently shown to induce exocytosis of synaptic vesicles following the production of lysophospholipids and fatty acids and a sustained influx of Ca(2+) from the medium. Here, we show that these toxins are able to penetrate spinal cord motor neurons and cerebellar granule neurons and selectively bind to mitochondria. As a result of this interaction, mitochondria depolarize and undergo a profound shape change from elongated and spaghetti-like to round and swollen. We show that snake presynaptic phospholipase A(2) neurotoxins facilitate opening of the mitochondrial permeability transition pore, an inner membrane high-conductance channel. The relative potency of the snake neurotoxins was similar for the permeability transition pore opening and for the phospholipid hydrolysis activities, suggesting a causal relationship, which is also supported by the effect of phospholipid hydrolysis products, lysophospholipids and fatty acids, on mitochondrial pore opening. These findings contribute to define the cellular events that lead to intoxication of nerve terminals by these snake neurotoxins and suggest that mitochondrial impairment is an important determinant of their toxicity.
Michela Rigoni; Marco Paoli; Eva Milanesi; Paola Caccin; Andrea Rasola; Paolo Bernardi; Cesare Montecucco
Related Documents :
25080475 - A nontumorigenic variant of fgf19 treats cholestatic liver diseases.
2807145 - The "survival hormones": azelaic and pimelic acids, suppress the stress elicited by iso...
1167335 - Alteration of fatty acid composition of lm cells by lipid supplementation and temperature.
1813115 - Effects of chronic alcohol ingestion on myocardial lipid and fatty acid composition in ...
22549395 - Caprylic acid precipitation method for impurity reduction: an alternative to convention...
16854025 - 2-hydroxypyridine <--> 2-pyridone tautomerization: catalytic influence of formic acid.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-09-22
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  283     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-12-01     Completed Date:  2009-02-04     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  34013-20     Citation Subset:  IM    
Dipartimento di Scienze Biomediche Sperimentali, Università di Padova and Istituto di Neuroscienze del Consiglio Nazionale delle Ricerche, Viale Giuseppe Colombo 3, I-35121 Padova, Italy.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Calcium / chemistry
Elapid Venoms / chemistry
Fatty Acids / chemistry
Lysophospholipids / chemistry
Mitochondria / drug effects,  metabolism*
Models, Biological
Neurons / metabolism*
Neurotoxins / chemistry
Phospholipases A2 / metabolism*
Rats, Wistar
Grant Support
Reg. No./Substance:
0/Elapid Venoms; 0/Fatty Acids; 0/Lysophospholipids; 0/Neurotoxins; 37223-96-4/notexin; 7440-70-2/Calcium; EC A2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  G9a and HP1 couple histone and DNA methylation to TNFalpha transcription silencing during endotoxin ...
Next Document:  Design of a conformationally defined and proteolytically stable circular mimetic of brain-derived ne...