Syin C, Parzy D, Traincard F, Boccaccio I, Joshi M B, Lin D T, Yang X M, Assemat K, Doerig C, Langsley G
Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD, USA.
Eur J Biochem. 2001 Sep;268(18):4842-9. doi: 10.1046/j.1432-1327.2001.02403.x.
In Plasmodium falciparum, the causative agent of human malaria, the catalytic subunit gene of cAMP-dependent protein kinase (Pfpka-c) exists as a single copy. Interestingly, its expression appears developmentally regulated, being at higher levels in the pathogenic asexual stages than in the sexual forms of parasite that are responsible for transmission to the mosquito vector. Within asexual parasites, PfPKA activity can be readily detected in schizonts. Similar to endogenous PKA activity of noninfected red blood cells, the parasite enzyme can be stimulated by cAMP and inhibited by protein kinase inhibitor.Importantly, ex vivo treatment of infected erythrocytes with the classical PKA-C inhibitor H89 leads to a block in parasite growth. This suggests that the PKA activities of infected red blood cells are essential for parasite multiplication. Finally, structural considerations suggest that drugs targeting the parasite, rather than the erythrocyte enzyme, might be developed that could help in the fight against malaria.
在人类疟疾的病原体恶性疟原虫中，环磷酸腺苷依赖性蛋白激酶的催化亚基基因（Pfpka-c）以单拷贝形式存在。有趣的是，其表达似乎受发育调控，在致病性无性阶段的水平高于负责传播至蚊媒的寄生虫有性形式。在无性寄生虫中，裂殖体中可轻易检测到PfPKA活性。与未感染红细胞的内源性PKA活性相似，寄生虫酶可被环磷酸腺苷刺激并被蛋白激酶抑制剂抑制。重要的是，用经典的PKA-C抑制剂H89对感染的红细胞进行体外处理会导致寄生虫生长受阻。这表明感染红细胞的PKA活性对寄生虫增殖至关重要。最后，从结构方面考虑，可能开发出针对寄生虫而非红细胞酶的药物，这有助于对抗疟疾。
