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恶性疟原虫配子体中端粒酶活性的鉴定。

Identification of telomerase activity in gametocytes of Plasmodium falciparum.

作者信息

Raj Dipak Kumar, Das Bibhu Ranjan, Dash A P, Supakar Prakash C

机构信息

Institute of Life Sciences, Chandrasekharpur, Bhubaneswar 751 023, India.

出版信息

Biochem Biophys Res Commun. 2003 Sep 26;309(3):685-8. doi: 10.1016/j.bbrc.2003.08.056.

DOI:10.1016/j.bbrc.2003.08.056
PMID:12963045
Abstract

Telomerase, a specialized cellular reverse transcriptase, compensates the chromosome shortening during the replication of most eukaryotic cells and contributes to cellular immortalization in cell culture (in vitro) and cancerous cell (in vivo). In the present study, the telomerase activity in the gametocytes of Plasmodium falciparum was investigated. Here, we report for the first time, the presence of telomerase activity in the gametocytes of P. falciparum using P. falciparum telomere repeat amplification protocol (Pf-TRAP) assay and Southern blot hybridization. Telomerase inhibitors such as 7-deaza-dGTP and AZT-TP, when used with the cytoplasmic extract of gametocytes in the Pf-TRAP assay, efficiently inhibit the product, which confirms the presence of telomerase in the gametocytes. The presence of telomerase activity in the laboratory adapted local (eastern India) isolates of P. falciparum indicates that telomerase might be the major player in chromosomal end protection during replication. The finding suggests that telomerase can be a potent target for the transmission blocking vaccine and drugs for combating malaria caused by P. falciparum.

摘要

端粒酶是一种特殊的细胞逆转录酶,可补偿大多数真核细胞复制过程中的染色体缩短,并在细胞培养(体外)和癌细胞(体内)中促进细胞永生化。在本研究中,对恶性疟原虫配子体中的端粒酶活性进行了研究。在此,我们首次使用恶性疟原虫端粒重复序列扩增协议(Pf-TRAP)测定法和Southern印迹杂交,报告了恶性疟原虫配子体中端粒酶活性的存在。端粒酶抑制剂,如7-脱氮-dGTP和AZT-TP,在Pf-TRAP测定法中与配子体的细胞质提取物一起使用时,可有效抑制产物,这证实了配子体中端粒酶的存在。实验室适应的本地(印度东部)恶性疟原虫分离株中端粒酶活性的存在表明,端粒酶可能是复制过程中染色体末端保护的主要参与者。这一发现表明,端粒酶可能是用于传播阻断疫苗和对抗恶性疟原虫引起的疟疾的药物的有力靶点。

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