title: Hemostatic and toxinological diversities in venom of Micrurus tener tener, Micrurus fulvius fulvius and Micrurus isozonus coral snakes.
abstract: The coral snake Micrurus tener tener (Mtt) from the Elapidae family inhabits the southwestern United States and produces severe cases of envenomations. Although the majority of Mtt venom components are neurotoxins and phospholipase A₂s, this study demonstrated, by SDS-PAGE and molecular exclusion chromatography (MEC), that these venoms also contain high-molecular-weight proteins between 50 and 150 kDa that target the hemostatic system. The biological aspects of other Micrurus venoms were also studied, such as the LD₅₀s of Micrurus isozonus (from 0.52 to 0.61 mg/kg). A pool from these venoms presented a LD₅₀ of 0.57 mg/kg, Micrurus f. fulvius (Mff) and Mtt had LD₅₀s of 0.32 and 0.78 mg/kg, respectively. These venoms contained fibrino(geno)lytic activity, they inhibited platelet aggregation, as well as factor Xa and/or plasmin-like activities. M. isozonus venoms from different Venezuelan geographical regions inhibited ADP-induced platelet aggregation (from 50 to 68%). Micrurus tener tener venom from the United States was the most active with a 95.2% inhibitory effect. This venom showed thrombin-like activity on fibrinogen and human plasma. Fractions of Mtt showed fibrino(geno)lytic activity and inhibition on plasmin amidolytic activity. Several fractions degraded the fibrinogen Aα chains, and fractions F2 and F7 completely degraded both fibrinogen Aα and Bβ chains. To our knowledge, this is the first report on thrombin-like and fibrino(geno)lytic activity and plasmin or factor Xa inhibitors described in Micrurus venoms. Further purification and characterization of these Micrurus venom components could be of therapeutic use in the treatment of hemostatic disorders.
authors: Laboratorio de Fisiopatología, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas (IVIC), Apartado 20632, Caracas 1020A, Venezuela.
authors: Ana M
authors: AM
authors: Salazar
authors: Jeilyn
authors: J
authors: Vivas
authors: Elda E
authors: EE
authors: Sánchez
authors: Alexis
authors: A
authors: Rodríguez-Acosta
authors: Carlos
authors: C
authors: Ibarra
authors: Amparo
authors: A
authors: Gil
authors: Zoila
authors: Z
authors: Carvajal
authors: María E
authors: ME
authors: Girón
authors: Amalid
authors: A
authors: Estrella
authors: Luis F
authors: LF
authors: Navarrete
authors: Belsy
authors: B
authors: Guerrero
references: Biochim Biophys Acta. 2000 Mar 7;1477(1-2):146-56
references: 10708855
references: Discov Med. 2009 Dec;8(43):242-6
references: 20040278
references: Curr Pharm Des. 2007;13(28):2906-15
references: 17979735
references: Toxicon. 1998 Dec;36(12):1749-800
references: 9839663
references: Biochemistry. 1993 Oct 12;32(40):10794-802
references: 8399228
references: PLoS Negl Trop Dis. 2010 Mar 09;4(3):e622
references: 20231886
references: Pathophysiol Haemost Thromb. 2005;34(4-5):200-4
references: 16707928
references: Toxicon. 2002 Jun;40(6):667-75
references: 12175602
references: Thromb Res. 1986 Apr 1;42(1):55-62
references: 3010494
references: Toxicon. 1992 Sep;30(9):1065-79
references: 1440644
references: Mol Biol Evol. 2005 Sep;22(9):1853-64
references: 15930152
references: Comp Biochem Physiol A Mol Integr Physiol. 2005 Jan;140(1):125-34
references: 15664321
references: Methods Enzymol. 1990;182:50-68
references: 2314256
references: Toxicon. 1982;20(2):501-4
references: 7080056
references: Biochim Biophys Acta. 2001 Jul 9;1548(1):57-65
references: 11451438
references: J Thromb Thrombolysis. 2010 Apr;29(3):340-8
references: 19629641
references: FEBS J. 2009 Jun;276(11):3163-75
references: 19490116
references: Biochemistry. 1990 Aug 21;29(33):7742-6
references: 2271532
references: Toxicon. 1983;21(6):777-83
references: 6658805
references: J Biochem. 1974 Oct;76(4):721-33
references: 4436285
references: Biochim Biophys Acta. 1991 Oct 26;1095(2):117-21
references: 1932133
references: Pharmacol Ther. 1994;62(3):325-72
references: 7972338
references: Toxicon. 2003 Jun;41(7):851-60
references: 12782085
references: Toxicon. 2005 Jun 15;45(8):1021-39
references: 15882884
references: J Toxicol Clin Toxicol. 2004;42(2):171-8
references: 15214622
references: Braz J Med Biol Res. 1991;24(7):701-10
references: 1823287
references: Toxicon. 2005 Jun 15;45(8):951-67
references: 15922768
references: Thromb Res. 2007;120(1):95-104
references: 17045631
references: Blood. 2003 Aug 15;102(4):1347-54
references: 12730119
references: Biochimie. 2000 Sep-Oct;82(9-10):851-9
references: 11086215
references: Toxicon. 2010 Sep 15;56(4):544-53
references: 20677373
references: Toxicon. 1996 Jul;34(7):807-19
references: 8843581
references: Comp Biochem Physiol C Toxicol Pharmacol. 2004 Aug;138(4):485-92
references: 15536056
references: Toxicon. 1997 Aug;35(8):1193-203
references: 9278969
references: Toxicon. 2009 Mar 1;53(3):375-82
references: 19135468
references: Mol Biosyst. 2010 Feb;6(2):305-15
references: 20094648
references: J Biochem Mol Biol. 2004 Mar 31;37(2):199-205
references: 15469696
references: Toxicon. 2003 Sep;42(3):239-47
references: 14559074
references: Biochimie. 2004 Mar;86(3):203-10
references: 15134835
references: Eur J Biochem. 1999 Jan;259(1-2):225-34
references: 9914497
references: Eur J Biochem. 1996 May 15;238(1):231-9
references: 8665942
references: Eur J Biochem. 1983 Jun 15;133(2):427-32
references: 6602050
references: Toxicon. 1996 Jun;34(6):627-42
references: 8817809
references: J Biol Chem. 1995 Apr 28;270(17):10246-55
references: 7730329
references: WHO Offset Publ. 1981;(58):1-44
references: 7245916
references: Toxicon. 2008 Feb;51(2):297-303
references: 18054059
references: Blood Coagul Fibrinolysis. 2000 Jun;11(4):385-93
references: 10847427
references: Biochemistry. 1994 Feb 22;33(7):1843-9
references: 8110787
references: Thromb Diath Haemorrh. 1972 Aug 31;28(1):75-88
references: 4672652
references: Toxicon. 2010 Feb-Mar;55(2-3):186-94
references: 19622365
references: Toxicon. 1992 Oct;30(10):1299-302
references: 1440634
references: Toxicon. 1992 Mar;30(3):265-93
references: 1529462
references: Toxicon. 1992 Aug;30(8):853-64
references: 1523677
references: Arch Biochem Biophys. 1999 Sep 1;369(1):107-13
references: 10462445
references: Comp Biochem Physiol C Toxicol Pharmacol. 2006 Jul;143(3):295-302
references: 16627005
references: Toxicon. 2007 Mar 1;49(3):293-8
references: 17141819
references: Toxicon. 1994 Apr;32(4):445-52
references: 8052999
references: Toxicon. 2001 Dec;39(12):1827-33
references: 11600144
references: Toxicon. 1999 Jan;37(1):11-32
references: 9920477
references: Biochim Biophys Acta. 1981 May 14;659(1):161-8
references: 6788089
references: Comp Biochem Physiol B. 1991;99(2):287-94
references: 1662592
references: Pathophysiol Haemost Thromb. 2005;34(4-5):184-7
references: 16707924
references: J Biol Chem. 1951 Nov;193(1):265-75
references: 14907713
references: Toxicon. 1994 Jun;32(6):713-23
references: 7940577
references: Toxicon. 2007 Dec 15;50(8):1064-72
references: 17822731
references: Thromb Res. 1992 May 1;66(2-3):169-77
references: 1412190