Induction of ferroptosis and mitochondrial dysfunction by oxidative stress in PC12 cells

Neurodegenerative diseases (NDD) are typically associated with neuron loss in nervous system areas. Interventions with related death mechanisms may ameliorate NDD progression. Oxidative stress plays an important role in NDD cell death routines. However, tert-butylhydroperoxide (t-BHP), a widely used oxidative stress stimulus, induces neural cell death through a mechanism that remains elusive. In our study, the ferroptosis marker events occurred after co-treatment with 100 μM t-BHP for 1 h, all of which were reversed in the presence of the ferroptosis inhibitor ferrostatin-1 (Fer-1) and the iron chelator deferoxamine, implying the occurrence of ferroptosis. Moreover, mitochondrial dysfunction accompanied by a decreased in membrane potential and ATP production, increased mitochondrial ROS generation. Furthermore, this mitochondrial dysfunction could be reversed by Fer-1. In addition, JNK1/2 and ERK1/2 were activated upstream of the ferroptosis and mitochondrial dysfunction. In summary, these data suggest that ferroptosis, coupled with mitochondrial dysfunction, was involved in t-BHP-induced PC12 death. JNK1/2 and ERK1/2 played important roles in t-BHP-induced cell death. Overall, this study might provide clues to the oxidative stress-based strategies for cell protection in NDD.

Medienart:

E-Artikel

Erscheinungsjahr:

2018

Erschienen:

2018

Enthalten in:

Zur Gesamtaufnahme - volume:8

Enthalten in:

Scientific reports - 8(2018), 1 vom: 12. Jan., Seite 574

Sprache:

Englisch

Beteiligte Personen:

Wu, Chuanhong [VerfasserIn]
Zhao, Wenwen [VerfasserIn]
Yu, Jie [VerfasserIn]
Li, Shaojing [VerfasserIn]
Lin, Ligen [VerfasserIn]
Chen, Xiuping [VerfasserIn]

Links:

Volltext

Themen:

8L70Q75FXE
955VYL842B
Adenosine Triphosphate
Cyclohexylamines
Deferoxamine
Ferrostatin-1
J06Y7MXW4D
Journal Article
Phenylenediamines
Reactive Oxygen Species
Research Support, Non-U.S. Gov't
Tert-Butylhydroperoxide

Anmerkungen:

Date Completed 27.11.2018

Date Revised 12.01.2019

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41598-017-18935-1

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM279927134