Mielniczki-Pereira A A, Chiavegatto C M, López J A, Colli W, Alves M J M, Gadelha F R
Departamento de Bioquímica, IB, UNICAMP, Campinas, SP, Brazil.
Acta Trop. 2007 Jan;101(1):54-60. doi: 10.1016/j.actatropica.2006.12.001. Epub 2006 Dec 16.
The drugs currently available for Chagas'disease treatment are unsatisfactory due to limited efficacy and toxic side effects, making the search for more specific pharmacological agents a priority. The components of the Trypanosoma cruzi trypanothione-dependent antioxidant system have been pointed out as potential chemotherapeutic targets for the development of more specific drugs. To work properly, this system must have a current supply of NADPH, provided by glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD). Here, we compare two T. cruzi strains, Tulahuen 2 and Y, regarding growth rate, cytosolic tryparedoxin peroxidase (TcCPX) concentration and pentose phosphate pathway dehydrogenases activities. Tulahuen 2 cells show higher values as compared to the Y strain when the following parameters are compared: TcCPX concentration, resistance to H2O2, growth index and G6PD activity. Different patterns of G6PD and 6PGD activities were observed among strains along the growth curve and when cells were challenged with H2O2. These data reinforce the heterogeneity within T. cruzi populations and also the importance of G6PD in protecting the parasite against reactive oxygen species.
目前可用于治疗恰加斯病的药物由于疗效有限和有毒副作用而不尽人意,因此寻找更具特异性的药理药物成为当务之急。克氏锥虫硫醇依赖型抗氧化系统的组成成分已被指出是开发更具特异性药物的潜在化疗靶点。为了正常工作,该系统必须有由葡萄糖-6-磷酸脱氢酶(G6PD)和6-磷酸葡萄糖酸脱氢酶(6PGD)提供的NADPH的当前供应。在此,我们比较了克氏锥虫的两个菌株,图拉亨2株和Y株,在生长速率、胞质硫氧还蛋白过氧化物酶(TcCPX)浓度和磷酸戊糖途径脱氢酶活性方面的差异。当比较以下参数时,图拉亨2株细胞与Y株相比显示出更高的值:TcCPX浓度、对H2O2的抗性、生长指数和G6PD活性。在沿生长曲线以及用H2O2刺激细胞时,各菌株之间观察到不同的G6PD和6PGD活性模式。这些数据强化了克氏锥虫群体内的异质性以及G6PD在保护寄生虫免受活性氧侵害方面的重要性。