College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, Jinzhong, 030801, China.
Parasitol Res. 2020 Aug;119(8):2549-2561. doi: 10.1007/s00436-020-06738-9. Epub 2020 Jun 20.
This study investigated the role of PI3K/Akt signaling pathway on host cell apoptosis in the early infection of Eimeria tenella. Chicken cecal epithelial cells were treated with apoptosis-inducer Actinomycin D (Act D) or PI3K/Akt signaling pathway inhibitor LY294002 and then infected with E. tenella. Results demonstrated that the E. tenella-infected group had less apoptosis 4-8 h after the infection and more apoptosis 12-20 h after the infection than the control group. At 4-20 h after the infection, the apoptotic/necrotic rate and the Caspase-3 activity in the Act D + E. tenella group were lower (P < 0.01) than those in the Act D-treated group. The p-Akt and NF-κB contents in the E. tenella-infected group were higher (P < 0.01) than those in the control group 4-12 h after the infection. However, the bad content and the Caspase-9/3 activity were lower (P < 0.05) in the E. tenella-infected group than in the control group. Compared with the E. tenella-infected group, the LY294002 + E. tenella group showed decreased p-Akt content and increased apoptotic/necrotic rate, bad content, NF-κB expression, membrane permeability transition pore (MPTP) openness, and Caspase-9/3 activity. Thus, the early development of E. tenella could inhibit host cell apoptosis by downregulating the Caspase-3 activity. Upregulating this activity promoted apoptosis. In addition, activating the PI3K/Akt signaling pathway inhibited the apoptosis of E. tenella host cells in the early infection by reducing the expression of the bad content, limiting the MPTP opening, and decreasing the Caspase-9 and Caspase-3 activities.
本研究旨在探讨 PI3K/Akt 信号通路在柔嫩艾美耳球虫早期感染宿主细胞凋亡中的作用。用凋亡诱导剂放线菌素 D(Act D)或 PI3K/Akt 信号通路抑制剂 LY294002 处理鸡回肠上皮细胞,然后感染柔嫩艾美耳球虫。结果表明,感染组在感染后 4-8 h 凋亡较少,在感染后 12-20 h 凋亡较多,与对照组相比。在感染后 4-20 h,Act D+柔嫩艾美耳球虫组的凋亡/坏死率和 Caspase-3 活性均较低(P<0.01),Act D 处理组。感染组的 p-Akt 和 NF-κB 含量在感染后 4-12 h 均高于对照组(P<0.01)。然而,感染组的 bad 含量和 Caspase-9/3 活性均低于对照组(P<0.05)。与感染组相比,LY294002+柔嫩艾美耳球虫组的 p-Akt 含量降低,凋亡/坏死率、bad 含量、NF-κB 表达、膜通透性转换孔(MPTP)开放度和 Caspase-9/3 活性增加。因此,柔嫩艾美耳球虫的早期发育可通过下调 Caspase-3 活性抑制宿主细胞凋亡。上调这种活性可促进凋亡。此外,激活 PI3K/Akt 信号通路可通过降低 bad 含量的表达、限制 MPTP 的开放以及降低 Caspase-9 和 Caspase-3 的活性,抑制早期感染中柔嫩艾美耳球虫宿主细胞的凋亡。