Suppression of JNK pathway protects neurons from oxidative injury via attenuating parthanatos in glutamate-treated HT22 neurons.

Oxidative stress causes diverse neurological disorders. Parthanatos is a type of programmed cell death, characterised by strong activation of poly (ADP-ribose) (PAR) polymerase-1 (PARP-1), PAR polymer accumulation, and nuclear translocation of apoptosis-inducing factor (AIF), and is involved in cellular oxidative injury. Signalling by c-Jun-N-terminal protein kinase (JNK) is activated by reactive oxygen species (ROS), and this also contributes to ROS production. However, the exact relationship between JNK signalling and parthanatos in neurological disorders triggered by oxidative stress is unclear. In this study, glutamate-treated HT22 neurons were used to investigate whether the signalling by JNK contributes a regulatory role to parthanatos in oxidative stress-related neurological disease. JNK signalling was activated in glutamate-treated HT22 neurons, demonstrated via upregulation of p-JNK levels. Pre-treatment with SP600125 markedly inhibited JNK signalling, increased cell viability, and significantly reversed PARP-1 overproduction, PAR polymer accumulation, and nuclear AIF translocation. In addition, inhibition of JNK signalling severely reduced the production of both intracellular ROS and mitochondria superoxide. This study indicated that parthanatos in glutamate-treated HT22 neurons could be suppressed by JNK signalling inhibition. JNK activation participated in parthanatos via an increase in intracellular ROS levels.