髓管氨酸相关蛋白6是一种离子通道相关的亲莱什曼酸酶
Shabina Parveen1, Saikat Majumder1, Neelam Bodhale2
1Department of Molecular Medicine, Bose Institute, CIT Scheme VII-M, Kolkata 700054. India.
与myotubularin相关的蛋白-6 (MTMR6) 被确定为内脏莱什曼病 (VL) 的关键酸酶. 沉默MTMR6降低了寄生虫负载和IL-10,为这种重新出现的疾病提供了新的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 寄生虫学的寄生虫学
- 分子生物学分子生物学
背景情况:
- 内脏莱什曼病 (VL) 是一种致命的,重新出现的疾病,由居住在巨细胞中的*Leishmania donovani*寄生虫引起.
- 由酶和酸酶调节的细胞内信号传递对于VL病变发生至关重要.
- 影响人体VL结果的特定酸酶以前是未知的.
研究的目的:
- 为了确定调节人体巨细胞内脏莱什曼病 (VL) 结果的酸酶.
- 为了研究肌管素相关蛋白-6 (MTMR6) 在*Leishmania donovani*感染中的作用.
主要方法:
- 在感染*L. donovani*的THP-1巨细胞中选人类酸酶siRNA库.
- 在感染后对巨细胞中MTMR6表达的分析,Toll-like受体 (TLR2) 刺激/阻断和米尔特福辛治疗.
- 在VL患者和特有对照中对MTMR6表达的比较.
主要成果:
- 鉴定出Myotubularin相关蛋白-6 (MTMR6) 是唯一的酸酶,其沉默降低了L. donovani的负载和IL-10的产生.
- 有毒的*L. donovani*感染和TLR2刺激增加了MTMR6的表达,而TLR2阻断和米尔特福辛治疗降低了它.
- 与特有对照组相比,未经治疗的VL患者的MTMR6水平较高,在米尔特福辛治疗后水平降低.
结论:
- MTMR6是第一个被确定的通过TLR2信号调节的离子通道相关酸酶,对VL有重大影响.
- MTMR6在Leishmania donovani感染和内脏莱什曼尼病的发病过程中发挥着至关重要的作用.
- 准MTMR6为内脏莱什曼病提供了潜在的治疗策略.
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