Role of Recombinant PnTx2-6 Protein as a Mediator of Vasodilation in Blood Vessels
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
The venome of Phoneutria nigriventer spider has been shown to have side effects including severe painful erections that last for hours. PnTx2-6, a toxin from P. nigriventer spider venom, modulates voltage gated Na+ channels and activation of nitric oxide (NO) production. NO is essential for the regulation of blood flow and pressure. Therefore, PnTx2-6 is expected to be effective not only for erectile dysfunction but also for cardiovascular diseases. A previously has reported cDNA clone for PnTx2-6 toxin, which was expressed in E. coli cytoplasm. We created the same clone and expressed it in a bacterial expression system. PnTx2-6 increased the genes expression of superoxide dismutase 1, glutathione peroxidase 1, and sulfiredoxin 1. We hypothesized that recombinant PnTx2-6 may indirectly regulate blood flow and pressure, resulting in NO production in human umbilical vein endothelial cells (HUVEC). These data suggest differential regulation of the vascular ageing process, which may contribute to the anatomic heterogeneity of atherosclerosis. The results of this study may be used for the emergency treatment of sudden cardiovascular disease caused by ageing.
Abstract
The venome of Phoneutria nigriventer spider has been shown to have side effects including severe painful erections that last for hours. PnTx2-6, a toxin from P. nigriventer spider venom, modulates voltage gated Na+ channels and activation of nitric oxide (NO) production. NO is essential for the regulation of blood flow and pressure. Therefore, PnTx2-6 is expected to be effective not only for erectile dysfunction but also for cardiovascular diseases. A previously has reported cDNA clone for PnTx2-6 toxin, which was expressed in E. coli cytoplasm. We created the same clone and expressed it in a bacterial expression system. PnTx2-6 increased the genes expression of superoxide dismutase 1, glutathione peroxidase 1, and sulfiredoxin 1. We hypothesized that recombinant PnTx2-6 may indirectly regulate blood flow and pressure, resulting in NO production in human umbilical vein endothelial cells (HUVEC). These data suggest differential regulation of the vascular ageing process, which may contribute to the anatomic heterogeneity of atherosclerosis. The results of this study may be used for the emergency treatment of sudden cardiovascular disease caused by ageing.
참고문헌 (13)
- Burnett AL, "Nitric oxide in the penis : physiology and pathology", J Urol, 157(1), pp.320~324 (1997)
- Hove CV, "Vasodilator efficacy of nitric oxide depends on mechanisms of intracellular calcium mobilization in mouse aortic smooth muscle cells", British Journal of Pharmacology, 158, pp.920~930 (2009)
- Cordeiro MN, "The purification and amino acid sequences of four Tx2 neurotoxins from the venom of the Brazilian"armed"spider Phoneutria nigriventer(Keys. )", FEBS, 310(2), pp.153~156 (1992)
- Diniz MRV, "Sequence of the DNA coding for the lethal neurotoxin Tx1 from the Brazilian"armed"spider Phoneutria nigriventer predicts the synthesis and processing of a preprotoxin", J Biol Chem, 268(21), pp.15340~15342 (1993)
- Jung AR, "The effect of PnTx2-6 protein from Phoneutria nigriventer spider toxin on improvement of erectile dysfunction in a rat model of cavernous nerve injury", Urology, 84(3), pp.730.e9~730.e17 (2014)
- Kalapothakis E, "Cloning of cDNAs encoding neurotoxic peptides from the spider Phoneutria nigriventer", Toxicon, 36(12), pp.1843~1850 (1998)
- Kalapothakis E, "Cloning, cDNA sequence analysis and patch clamp studies of a toxin from the venom of the spider Phoneutria nigriventer", Toxicon, 36(12), pp.1971~1980 (1998)
- Barton M, "Anatomic heterogeneity of vascular aging : role of nitric oxide and endothelin", Hypertension, 30(4), pp.817~824 (1997)
- Nunes KP, "Nitric oxide-induced vasorelaxation in response to PnTx2-6 toxin from Phoneutria nigriventer spider in rat cavernosal tissue", J Sex Med, 7(12), pp.3879~3888 (2010)
- Schenberg S, "Pharmacology of the polypeptides from the venom of the spider Phoneutria fera. Mem. Inst", Butantan, 33(2), pp.627~638 (1966)
- Torres FS, "Functional expression of a recombinant toxin-rPnTx2-6-active in erectile function in rat", Toxicon, 56(7), pp.1172~1180 (2010)
- Vital Brazil O, "Modo de ação da peçonha de armadeira (Phoneutria nigriventer) na aurícula isolada de cobaia", Reunião Anual da Federação das Sociedades de Biologia Experimental 2, ~ (1987)
- Yoon Y, "Plasma Nitric Oxide Concentrations and Nitric Oxide Synthase Gene Polymorphisms in Coronary Artery Disease", Clin Chem, 46(10), pp.1626~1630 (2000)
