关键词: Babesia gibsoni Geldanamycin Heat shock protein 90 Tanespimycin

Mesh : Animals Dogs Babesia Superoxides / metabolism HSP90 Heat-Shock Proteins / metabolism Hypoxanthines / metabolism pharmacology Cell Proliferation Dog Diseases / parasitology Babesiosis / parasitology

来  源:   DOI:10.1016/j.exppara.2023.108567

Abstract:
The present study investigated the role of heat shock protein 90 (HSP90) in the proliferation and survival of Babesia gibsoni in vitro. To detect the effect on the entry of B. gibsoni into host erythrocytes, the parasite was incubated with an antibody against B. gibsoni HSP90 (BgHSP90) for 24 h. The results of this experiment demonstrated that both the incorporation of [3H]hypoxanthine into the nucleic acids of B. gibsoni and the number of parasites were not altered, indicating that an anti-BgHSP90 antibody did not directly inhibit the entry of the parasite into erythrocytes. Moreover, two HSP90 inhibitors, geldanamycin (GA) and tanespimycin (17-AAG), were used to evaluate the function of BgHSP90. GA and 17-AAG decreased both the incorporation of [3H]hypoxanthine and the number of infected erythrocytes, suggesting that BgHSP90 plays important roles in DNA synthesis and the proliferation of B. gibsoni. The effect of 17-AAG on the parasites was weaker than that of GA. Additionally, the effect of GA on the survival and superoxide generation of canine neutrophils was assessed. The survival of canine neutrophils was not affected. The superoxide generation was strongly suppressed by GA. This result indicated that GA inhibited the function of canine neutrophils. Additional studies are necessary to elucidate the role of BgHSP90 in the proliferation of the parasite.
摘要:
本研究研究了热休克蛋白90(HSP90)在体外生长和存活中的作用。为了检测对双歧杆菌进入宿主红细胞的影响,将寄生虫与针对吉布氏芽孢杆菌HSP90(BgHSP90)的抗体一起孵育24小时。该实验的结果表明,[3H]次黄嘌呤掺入到B.gibsoni的核酸和寄生虫的数量都没有改变,表明抗BgHSP90抗体不能直接抑制寄生虫进入红细胞.此外,两种HSP90抑制剂,格尔德霉素(GA)和坦西霉素(17-AAG),用于评估BgHSP90的功能。GA和17-AAG降低了[3H]次黄嘌呤的掺入和感染的红细胞数量,提示BgHSP90在Gibsoni的DNA合成和增殖中起重要作用。17-AAG对寄生虫的作用弱于GA。此外,评估了GA对犬中性粒细胞存活和超氧化物生成的影响.犬中性粒细胞的存活没有受到影响。超氧化物的产生受到GA的强烈抑制。该结果表明GA抑制犬中性粒细胞的功能。需要进一步的研究来阐明BgHSP90在寄生虫增殖中的作用。
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