Transient receptor potential channel 6 knockdown prevents apoptosis of renal tubular epithelial cells upon oxidative stress via autophagy activation

• Autores: Hou, Xin; Xiao, Haitao; Zhang, Yanhong; Zeng, Xixi; Huang, Mengjun; Chen, Xiaoyun; Birnbaumer, Lutz; Liao, Yanhong
• Año de publicación: 2018
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Cell Death & Disease. 2018;9(10):1-15
• Materia: RIÑON; ESTRES OXIDATIVO; APOPTOSIS; CELULAS EPITELIALES; INSUFICIENCIA RENAL
• Institución: Pontificia Universidad Católica Argentina

Fil: Hou, Xin. Huazhong University of Science and Technology. Tongji Medical College. Department of Anatomy; China
Fil: Hou, Xin. Hebei University of Engineering. Affiliated Hospital. Medical College. Department of Anatomy; China
Fil: Xiao, Haitao. Huazhong University of Science and Technology. Tongji Medical College. Department of Anatomy; China
Fil: Xiao, Haitao. Huazhong University of Science and Technology. Tongji Medical College. Key Laboratory of Neurological Diseases of Ministry of Education; China
Fil: Zhang, Yanhong. Huazhong University of Science and Technology. Tongji Medical College. Department of Anatomy; China
Fil: Zhang, Yanhong. Huazhong University of Science and Technology. Tongji Medical College. Key Laboratory of Neurological Diseases of Ministry of Education; China
Fil: Zeng, Xixi. Huazhong. University of Science and Technology. Tongji Medical College. Department of Anatomy; China
Fil: Zeng, Xixi. Huazhong. University of Science and Technology. Tongji Medical College. Key Laboratory of Neurological Diseases of Ministry of Education; China
Fil: Huang, Mengjun. University of Science and Technology. Tongji Medical College. Department of Anatomy; China
Fil: Huang, Mengjun. University of Science and Technology. Tongji Medical College. Key Laboratory of Neurological Diseases of Ministry of Education; China
Fil: Chen, Xiaoyun. First Hospital of Wuhan. Department of Pathology; China
Fil: Birnbaumer, Lutz. Research Triangle Park. National Institute of Environmental Health Sciences. Neurobiology Laboratory; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Liao, Yanhong. Huazhong University of Science and Technology. Tongji Medical College. Department of Anatomy; China
Fil: Liao, Yanhong. Huazhong University of Science and Technology. Tongji Medical College. Department of Anatomy; China
Abstract: Reactive oxygen species (ROS) are generated under various pathological conditions such as renal ischemia/reperfusion (I/R) injury and provoke damage to multiple cellular organelles and processes. Overproduction of ROS causes oxidative stress and contributes to damages of renal proximal tubular cells (PTC), which are the main cause of the pathogenesis of renal I/R injury. Autophagy is a dynamic process that removes long-lived proteins and damaged organelles via lysosome-mediated degradation, which has an antioxidant effect that relieves oxidative stress. The canonical transient receptor potential channel 6 (TRPC6), a nonselective cation channel that allows passage of Ca2+, plays an important role in renal disease. Yet, the relationship between TRPC6 and autophagy, as well as their functions in renal oxidative stress injury, remains unclear. In this study, we found that oxidative stress triggered TRPC6-dependent Ca2+ influx in PTC to inhibit autophagy, thereby rendering cells more susceptible to death. We also demonstrated that TRPC6 knockout (TRPC6-/-) or inhibition by SAR7334, a TRPC6-selective inhibitor, increased autophagic flux and mitigated oxidative stress-induced apoptosis of PTC. The protective effects of TRPC6 ablation were prevented by autophagy inhibitors Chloroquine and Bafilomycin A1. Moreover, this study also shows that TRPC6 blockage promotes autophagic flux via inhibiting the PI3K/Akt/mTOR and ERK1/2 signaling pathways. This is the first evidence showing that TRPC6-mediated Ca2+ influx plays a novel role in suppressing cytoprotective autophagy triggered by oxidative stress in PTC, and it may become a novel therapeutic target for the treatment of renal oxidative stress injury in the future.