Actions of a proline analogue, L-thiazolidine-4-carboxylic acid (T4C), on Trypanosoma cruzi.
Actions of a proline analogue, L-thiazolidine-4-carboxylic acid (T4C), on Trypanosoma cruzi.
复制标题
DOI：
10.1371/journal.pone.0004534
复制
发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Silber AM
中科院分区：
文献类型：
--
作者：
Magdaleno A;Ahn IY;Paes LS;Silber AM
已确定L-脯氨酸在锥虫生物学中具有多种作用。在克氏锥虫（锥虫病的病原体）中，这种氨基酸参与能量代谢、分化过程和对渗透胁迫的抗性。在这项研究中，我们分析了干扰L-脯氨酸代谢对T. cruzi生命周期中使用脯氨酸类似物L-噻唑烷-4-羧酸（T4 C）。使用不同浓度的T4 C在标准培养条件下，在高温或酸性pH值的epimastigotes的生长进行了评估。我们还评估了这种类似物与应力条件下，如营养饥饿和氧化应激产生的可能的相互作用。T4 C显示出对外鞭毛体生长的剂量反应效应（IC 50 = 0.89±0.02 mM，28°C），并且该类似物的抑制效应与温度（0.54±0.01 mM，37°C）协同（p<0.05）。 T4 C与营养饥饿和氧化应激条件组合显著降低寄生虫存活（p<0.05）。预孵育的寄生虫与L-脯氨酸导致对氧化应激的保护作用，但这是没有看到在药物的存在。最后，从感染的哺乳动物细胞的锥虫鞭毛体爆裂进行了评估，发现被抑制高达56%，当细胞用无毒浓度的T4 C（1和10 mM之间）。所有这些数据都表明，如果与其他影响氧化应激的药物结合，T4 C可能是一种有趣的治疗药物。这些数据也支持脯氨酸代谢参与抗氧化胁迫。
It is well established that L-proline has several roles in the biology of trypanosomatids. In Trypanosoma cruzi, the etiological agent of Chagas' disease, this amino acid is involved in energy metabolism, differentiation processes and resistance to osmotic stress. In this study, we analyzed the effects of interfering with L-proline metabolism on the viability and on other aspects of the T. cruzi life cycle using the proline analogue L- thiazolidine-4-carboxylic acid (T4C). The growth of epimastigotes was evaluated using different concentrations of T4C in standard culture conditions and at high temperature or acidic pH. We also evaluated possible interactions of this analogue with stress conditions such as those produced by nutrient starvation and oxidative stress. T4C showed a dose-response effect on epimastigote growth (IC50 = 0.89±0.02 mM at 28°C), and the inhibitory effect of this analogue was synergistic (p<0.05) with temperature (0.54±0.01 mM at 37°C). T4C significantly diminished parasite survival (p<0.05) in combination with nutrient starvation and oxidative stress conditions. Pre-incubation of the parasites with L-proline resulted in a protective effect against oxidative stress, but this was not seen in the presence of the drug. Finally, the trypomastigote bursting from infected mammalian cells was evaluated and found to be inhibited by up to 56% when cells were treated with non-toxic concentrations of T4C (between 1 and 10 mM). All these data together suggest that T4C could be an interesting therapeutic drug if combined with others that affect, for example, oxidative stress. The data also support the participation of proline metabolism in the resistance to oxidative stress.
登录
查看更多内容
DOI：
10.4269/ajtmh.1998.59.166
发表时间：
1998-07-01
影响因子：
3.3
作者：
Kollien, AH;Schaub, GA
通讯作者：
Schaub, GA
影响因子：
2.2
作者：
Kollien, AH;Grospietsch, T;Schaub, GA
通讯作者：
Schaub, GA
影响因子：
7.4
作者：
Krishnan, Navasona;Dickman, Martin B.;Becker, Donald F.
通讯作者：
Becker, Donald F.
影响因子：
7.4
作者：
ELTHON, TE;STEWART, CR
通讯作者：
STEWART, CR
影响因子：
1.3
作者：
ASIN, S;CATALA, S
通讯作者：
CATALA, S