Secretory phospholipase A2 potentiates glutamate-induced rat striatal neuronal cell death in vivo.
The secretory phospholipases A2 (sPLA2) OS2 (10, 20 and 50 pmol) or OS1, (50 pmol) purified from taipan snake Oxyuranus scutellatus scutellatus venom, and the excitatory amino acid glutamate (Glu) (2.5 and 5.0 micromol) were injected into the right striatum of male Wistar rats. Injection of 10 and 20 pmol OS2 caused no neurological abnormalities or tissue damage. OS2 (50 pmol) caused apathy and circling towards the injection side. Histology revealed an infarct at the injection site. Injection of 50 pmol OS1 showed very little or no signs of neurotoxicity. Injection of 2.5 micromol Glu caused no tissue damage or neurological abnormality. After injection of 5.0 micromol Glu, the animals initially circled towards the side of injection, and gradually developed generalized clonic convulsions. These animals showed a well demarcated striatal infarct. When non-toxic concentrations of 20 pmol OS2 and 2.5 micromol Glu were co-injected, a synergistic neurotoxicity was observed. Extensive histological damage occurred in the entire right hemisphere, and in several rats comprising part of the contralateral hemisphere. These animals were apathetic in the immediate hours following injection, with circling towards the side of injection in the following days. Thus, OS2 greatly potentiates glutamate excitoxicity in vivo.
Kolko
M
M
Laboratory of Neuropathology, University of Copenhagen, Denmark.
Bruhn
T
T
Christensen
T
T
Lazdunski
M
M
Lambeau
G
G
Bazan
N G
NG
Diemer
N H
NH
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D002544:Cerebral Infarction / Q000139:chemically induced / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology*; D004546:Elapid Venoms / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009474:Neurons / Q000166:cytology* / Q000201:enzymology; D009498:Neurotoxins / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism* / Q000494:pharmacology; D054467:Phospholipases A2; D051381:Rats; D017208:Rats, Wistar; D030162:Reptilian Proteins
D004546:Elapid Venoms; D009498:Neurotoxins; D030162:Reptilian Proteins; D018698:Glutamic Acid; D010741:Phospholipases A; C073206:Oxyuranus scutellatus toxin 2; D054467:Phospholipases A2