ANOPHELES STEPHENSI NO SYNTHASE--IMPACT ON PLASMODIUM

按蚊无合酶——对疟原虫的影响

• 批准号: 2005574
• 负责人: Shirley Luckhart
• 金额: $ 7.51万
• 依托单位: HENRY M. JACKSON FDN FOR THE ADV MIL/MED
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2005574
• 关键词: Culicidae; Plasmodium; arthropod borne communicable disease; catalyst; chimeric proteins; communicable disease control; computer assisted sequence analysis; disease vectors; enzyme activity; enzyme biosynthesis; enzyme linked immunosorbent assay; gel mobility shift assay; gene expression; host organism interaction; malaria; molecular cloning; nitric oxide synthase; northern blottings; nucleic acid sequence; polymerase chain reaction; southern blotting; toxin

Vertebrate nitric oxide synthase (NOS) isoforms catalyze nitric oxide (NO) production for neuronal signalling, vasodilation, and destruction of pathogens, including liver-invading sporozoites of Plasmodium spp., the causative agents of malaria. Recent results from this laboratory indicate that Anopheles stephensi, a natural vector of Plasmodium, possesses a NOS gene (AsNOS) with striking homology to the recently described Drosophila NOS gene. Reverse transcriptase-polymerase chain reaction assays indicate that AsNOS is synthesized during P. falciparum and P. berghei infections, suggesting that anorpheline mosquitoes may possess an analogous NO killing mechanism for Plasmodium. Two objectives have been proposed for the characterization of AsNOS: (1) clone, sequence, and analyze enzyme activity of AsNOS, and (2) demonstrate NO toxicity to mosquito stage Plasmodium in vitro and in vivo. Sequence of full-length AsNOS and associated upstream regions will confirm the identity of AsNOS, provide insight into regulation of its expression, and facilitate construction of an expression system for enzyme analysis. Catalysis of NO production by AsNOS in vitro will confirm its behavior as a NOS isoform. Characterization of AsNOS in vitro will confirm its behavior as a NOS isoform. Characterization of AsNOS and its activity will provide new insights into mosquito-parasite biology, provide tools with which to examine NOS in other insect vectors, and perhaps provide a novel basis for engineering Plasmodium-refractory mosquitoes to interrupt the transmission of human malaria parasites.

脊椎动物一氧化氮合成酶（NOS）异构体催化一氧化氮（NO）