Isolation and characterization of "Reprotoxin", a novel protein complex from Daboia russelii snake venom.
In snake venoms, non-covalent protein-protein interaction leads to protein complexes with synergistic and, at times, distinct pharmacological activities. Here we describe a new protein complex containing phospholipaseA(2) (PLA(2)), protease, and a trypsin inhibitor. It is isolated from the venom of Daboia russelii by gel permeation chromatography, on a Sephadex G-75 column. This 44.6 kDa complex exhibits only phospholipase A(2) activity. In the presence of 8M urea it is well resolved into protease (29.1 kDa), PLA(2) (13 kDa), and trypsin inhibitor (6.5 kDa) peaks. The complex showed an LD(50) of 5.06 mg/kg body weight in mice. It inhibited the frequency of spontaneous release of neurotransmitter in hippocampal neurons. It also caused peritoneal bleeding, and edema in the mouse foot pads. Interestingly, the complex caused degeneration of both the germ cells and the mouse Leydig cells of mouse testis. A significant reduction in both the diameter of the seminiferous tubules and height of the seminiferous epithelia were observed following intraperitoneal injection of the sub-lethal dose (3 mg/kg body weight). This effect of the toxin is supported by the increase in the activities of acid and alkaline phosphatases and the nitric oxide content in the testes, and a decrease in the ATPase activity. Because of its potent organ atrophic effects on the reproductive organs, the toxin is named "Reprotoxin". This is the first report demonstrating toxicity to the reproductive system by a toxin isolated from snake venom.
Department of Biochemistry, University of Mysore, Manasagangothri, Mysore, India.
J R
JR
Kumar
Balapal S
BS
Basavarajappa
Ottavio
O
Arancio
Ivan
I
Aranha
N S
NS
Gangadhara
H N
HN
Yajurvedi
T Veerabasappa
TV
Gowda
D000818:Animals; D001284:Atrophy / Q000139:chemically induced; D006470:Hemorrhage / Q000139:chemically induced; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D007928:Lethal Dose 50; D007985:Leydig Cells / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D010447:Peptide Hydrolases / Q000302:isolation & purification / Q000633:toxicity; D010529:Peritoneal Cavity / Q000473:pathology; D054467:Phospholipases A2 / Q000302:isolation & purification / Q000633:toxicity; D011506:Proteins / Q000302:isolation & purification* / Q000633:toxicity*; D012671:Seminiferous Tubules / Q000187:drug effects / Q000473:pathology; D012708:Sertoli Cells / Q000187:drug effects / Q000473:pathology; D013737:Testis / Q000187:drug effects; D014361:Trypsin Inhibitors / Q000302:isolation & purification / Q000633:toxicity; D014757:Viper Venoms / Q000737:chemistry*; D017819:Viperidae
D011506:Proteins; D014361:Trypsin Inhibitors; D014757:Viper Venoms; D016202:N-Methylaspartate; D054467:Phospholipases A2; D010447:Peptide Hydrolases