Caspase-8 Regulates Endoplasmic Reticulum Stress-Induced Necroptosis Independent of the Apoptosis Pathway in Auditory Cells

• Published in: International journal of molecular sciences Vol. 20; no. 23; p. 5896
• Main Authors: Kishino, Akihiro, Hayashi, Ken, Maeda, Miyoko, Jike, Toyoharu, Hidai, Chiaki, Nomura, Yasuyuki, Oshima, Takeshi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.11.2019; MDPI
• Subjects: Amino Acid Chloromethyl Ketones - pharmacology; Animals; Apoptosis; Apoptosis - drug effects; Caspase 3 - metabolism; Caspase 8 - chemistry; Caspase 8 - genetics; Caspase 8 - metabolism; Caspase 9 - chemistry; Caspase 9 - genetics; Caspase 9 - metabolism; Caspase inhibitors; Caspase-3; Caspase-8; Caspase-9; Cell death; Cell Line; Cell Survival - drug effects; Ear protection; Endoplasmic reticulum; Endoplasmic Reticulum Stress - drug effects; Flow cytometry; Hair Cells, Auditory - cytology; Hair Cells, Auditory - metabolism; Hair Cells, Auditory - ultrastructure; Hearing loss; Inner ear; Investigations; Kinases; Mice; Morphology; Necroptosis; Pathogenesis; Protein-serine/threonine kinase; Proteins; Receptor-Interacting Protein Serine-Threonine Kinases - antagonists & inhibitors; Receptor-Interacting Protein Serine-Threonine Kinases - genetics; Receptor-Interacting Protein Serine-Threonine Kinases - metabolism; RNA Interference; RNA, Small Interfering - metabolism; Therapeutic targets; Transmission electron microscopy; Tunicamycin; Tunicamycin - pharmacology; apoptosis; auditory cells; endoplasmic reticulum stress; necroptosis

The aim of this study is to elucidate the detailed mechanism of endoplasmic reticulum (ER) stress-induced auditory cell death based on the function of the initiator caspases and molecular complex of necroptosis. Here, we demonstrated that ER stress initiates not only caspase-9-dependent intrinsic ap...