Double-stranded RNA-dependent protein kinase (PKR) is a component of signal transduction pathways mediating various stress signals including oxidative stress and endoplasmic reticulum (ER) stress and is suggested to be implicated in several neurodegenerative diseases. Cell death in neurodegenerative conditions has been linked to oxidative stress; however, the involvement of PKR in endogenous oxidative stress such as oxytosis and ferroptosis which is quite distinct from classical apoptosis remains unknown. We investigated here the effect of a PKR inhibitor C16 (an imidazole-oxindole derivative) on oxytosis and ferroptosis in cultured HT22 mouse hippocampal cells. C16 prevented glutamate- and erastin-induced cell death, reactive oxygen species accumulation, Ca2+ influx, phosphorylation of inositol-requiring enzyme 1 (IRE1), one of the three branches of ER stress signaling and its downstream signaling components. On the other hand, C16 did not prevent oxidative stress-induced heme oxygenase-1 expression; instead, C16 activated the extracellular signal-regulated kinase pathway. The protective effect of C16 is diminished in PKR knockout HT22 cells. Real time measurements of the oxygen consumption rate and extracellular acidification rate over a long period of time leading to cell death showed that C16 partially prevented erastin-induced mitochondrial and glycolytic dysfunction. These results suggest that PKR is an important component of oxytosis and ferroptosis and the inhibition of PKR is neuroprotective against endogenous oxidative stress-induced cell death and provide an effective strategy for neuroprotection.
Pubmed ID: 30817950 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Commercial antibody vendor which supplies antibodies and other products to life science researchers.
View all literature mentionsPrivately held company that develops and produces antibodies, ELISA kits, ChIP kits, proteomic kits, and other related reagents used to study cell signaling pathways that impact human health.
View all literature mentionsThis polyclonal targets Phospho-SAPK/JNK (Thr183/Tyr185)
View all literature mentionsThis monoclonal targets HO-1 mAb (HO-1-1)
View all literature mentionsThis monoclonal targets anti GAPDH (Loading Control)
View all literature mentionsThis polyclonal targets p38 MAPK, phospho (Thr180 / Tyr182)
View all literature mentionsThis polyclonal targets IRE1 alpha
View all literature mentionsThis monoclonal targets Phospho-PERK (Thr980)
View all literature mentionsThis monoclonal targets Phospho-MEK1/2 (Ser217/221)
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsCell line HT22 is a Transformed cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsThis polyclonal targets Phospho-SAPK/JNK (Thr183/Tyr185)
View all literature mentionsThis monoclonal targets HO-1 mAb (HO-1-1)
View all literature mentions