Purification, characterization and cytokine release function of a novel Arg-49 phospholipase A(2) from the venom of Protobothrops mucrosquamatus.
Group IIA phospholipase A(2) (PLA(2)) are major components in Viperidae/Crotalidae venom. In the present study, a novel PLA(2) named promutoxin with Arg at the site 49 has been purified from the venom of Protobothrops mucrosquamatus by chromatography. It consists of 122 amino acid residues with a molecular mass of 13,656 Da assessed by MALDI-TOF. It has the structural features of snake venom group IIA PLA(2)s, but has no PLA(2) enzymatic activity. Promutoxin shows higher amino acid sequence identity to the K49 PLA(2)s (72-95%) than to D49 PLA(2)s (52-58%). Promutoxin exhibits potent myotoxicity in the animal model with as little as 1 microg of promutoxin causing myonecrosis and myoedema in the gastrocnemius muscle of mice. Promutoxin is also able to stimulate the release of IL-12, TNFalpha, IL-6 and IL-1beta from human monocytes, and induce IL-2, TNFalpha and IL-6 release from T cells, indicating that this snake venom group IIA PLA(2) is actively involved in the inflammatory process in man caused by snake venom poisoning.
Wei
Ji-Fu
JF
Allergy and Inflammation Research Institute, The Shantou University Medical College, Xinling Road 11, 515031 Shantou, Guangdong, China.
Li
Tao
T
Wei
Xiao-Long
XL
Sun
Qian-Yun
QY
Yang
Fu-Mei
FM
Chen
Qiu-Yu
QY
Wang
Wan-Yu
WY
Xiong
Yu-Liang
YL
He
Shao-Heng
SH
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001120:Arginine; D001483:Base Sequence; D003435:Crotalid Venoms / Q000201:enzymology*; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D010741:Phospholipases A / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000900:Anti-Bacterial Agents; D003435:Crotalid Venoms; D016207:Cytokines; D001120:Arginine; D010741:Phospholipases A