First egg protein with a neurotoxic effect on mice.
While many invertebrates sequester toxic compounds to endow eggs with chemical defences, here we show, for the first time to our knowledge, the identification of a neurotoxin of proteinaceous nature localized inside an egg. Egg extracts from the freshwater apple snail Pomacea canaliculata displayed a neurotoxic effect in mice upon intraperitoneal injection (i.p.) (LD50, 96h 2.3mg/kg). Egg protein and total lipids were analysed separately and the only fraction displaying a highly toxic effect (LD50, 96h 0.25mg/kg, i.p.) was further purified to homogeneity as an oligomeric glyco-lipoprotein of 400kDa and two subunits biochemically and immunologically indistinguishable from the previously described perivitellin PV2. The neurotoxin was heat sensitive and there was evidence of circulating antibody response to sublethal i.p. doses on mice. Clinical signs, histopathological and immunocytochemical studies revealed damage mostly in mice spinal cord. Experiments showed chromatolysis and a decreased response to calbindin D-28K associated with a significant increase of TUNEL-positive cells in the dorsal horn neurons. These results suggest that calcium buffering and apoptosis may play a role in the neurological disorders induced by the toxin in mammalian central nervous system. This is the first report of a mollusc neurotoxin genetically encoded outside the cone-snail species.
Heras
Horacio
H
Instituto de Investigaciones Bioquímicas de La Plata, Facultad de Medicina, CONICET-Universidad Nacional de La Plata, Calles 60 y 120, 1900 La Plata, Argentina. h-heras@atlas.med.unlp.edu.ar
Frassa
M Victoria
MV
Fernández
Patricia E
PE
Galosi
Cecilia M
CM
Gimeno
Eduardo J
EJ
Dreon
Marcos S
MS
D000818:Animals; D064026:Calbindins; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects* / Q000473:pathology; D004527:Egg Proteins / Q000633:toxicity*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064030:S100 Calcium Binding Protein G; D012908:Snails / Q000378:metabolism*
D064026:Calbindins; D002135:Calcium-Binding Proteins; D004527:Egg Proteins; D009419:Nerve Tissue Proteins; D064030:S100 Calcium Binding Protein G