Trichomonas vaginalis induces apoptosis via ROS and ER stress response through ER-mitochondria crosstalk in SiHa cells

• Published in: Parasites & vectors 2021-12, Vol.14 (1), p.603-603, Article 603
• Main Authors: Gao, Fei Fei, Quan, Juan-Hua, Lee, Min A, Ye, Wei, Yuk, Jae-Min, Cha, Guang-Ho, Choi, In-Wook, Lee, Young-Ha
• Format: Article
• Language: English
• Subjects: Antibodies; Apoptosis; Bcl-2 protein; c-Jun protein; Cell Line, Tumor; Cells; Cellular stress response; Cervical cancer; Cervix; Complications and side effects; Crosstalk; Cytotoxicity; Depolarization; Development and progression; Dyes; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum Stress; Enzymes; Female; Flow cytometry; Health aspects; Human cervical cancer SiHa cells; Humans; Immunocytochemistry; Infections; Inhibitors; Iodides; JNK protein; Kinases; Laboratories; Lesions; MAP kinase; Medical research; Membrane potential; Membrane Potential, Mitochondrial; Mitochondria; Mitochondria - metabolism; Mitochondrial apoptosis; Molecular modelling; Mucosa; Oxidative stress; Parasites; Parasitic diseases; Pathogenesis; Phenylbutyric acid; Phosphorylation; Physiological aspects; Pretreatment; Proteins; Reactive oxygen species; Reactive Oxygen Species - metabolism; Risk factors; Secretory products; Sexually transmitted diseases; Signal Transduction; STD; Time dependence; Transcription factors; Trichomonas vaginalis; Trichomonas vaginalis - physiology; Trichomoniasis; Uterine Cervical Neoplasms - parasitology; Western blotting; Women
• ISSN: 1756-3305; 1756-3305
• DOI: 10.1186/s13071-021-05098-2

Trichomonas vaginalis causes lesions on the cervicovaginal mucosa in women; however, its pathogenesis remains unclear. We have investigated the involvement of the endoplasmic reticulum (ER) in the induction of apoptosis by T. vaginalis and its molecular mechanisms in human cervical cancer SiHa cells. Apoptosis, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), ER stress response and Bcl-2 family protein expression were evaluated using immunocytochemistry, flow cytometry, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide dye staining and western blotting. Trichomonas vaginalis induced mitochondrial ROS production, apoptosis, the ER stress response and mitochondrial dysfunction, such as MMP depolarization and an imbalance in Bcl-2 family proteins, in SiHa cells in a parasite burden- and infection time-dependent manner. Pretreatment with N-acetyl cysteine (ROS scavenger) or 4-phenylbutyric acid (4-PBA; ER stress inhibitor) significantly alleviated apoptosis, mitochondrial ROS production, mitochondrial dysfunction and ER stress response in a dose-dependent manner. In addition, T. vaginalis induced the phosphorylation of apoptosis signal regulating kinase 1 (ASK1) and c-Jun N-terminal kinases (JNK) in SiHa cells, whereas 4-PBA or SP600125 (JNK inhibitor) pretreatment significantly attenuated ASK1/JNK phosphorylation, mitochondrial dysfunction, apoptosis and ER stress response in SiHa cells, in a dose-dependent manner. Furthermore, T. vaginalis excretory/secretory products also induced mitochondrial ROS production, apoptosis and the ER stress response in SiHa cells, in a time-dependent manner. Trichomonas vaginalis induces apoptosis through mitochondrial ROS and ER stress responses, and also promotes ER stress-mediated mitochondrial apoptosis via the IRE1/ASK1/JNK/Bcl-2 family protein pathways in SiHa cells. These data suggest that T. vaginalis-induced apoptosis is affected by ROS and ER stress response via ER-mitochondria crosstalk.