Inhibition of mitochondrial calcium uniporter protects neurocytes from ischemia/reperfusion injury via the inhibition of excessive mitophagy

Copyright © 2016 Elsevier Ireland Ltd. All rights reserved..

Mitophagy plays an important role in mitochondrial quality control and cell survival during the process of ischemia/reperfusion (I/R) injury. Mitochondrial calcium uniporter (MCU) is the most important channel responsible for Ca(2+) influx into mitochondria and Ca(2+) signal plays a potential role in modulating mitophagy. However, the effect of MCU on mitophagy during the process of I/R injury remains unknown. This study constructed an in vitro I/R model by subjecting oxygen and glucose deprivation/reperfusion (OGD/RP) model to SH-SY5Y cells to mimic the cerebral I/R injury and aimed to explore the exact effect of MCU on I/R induced mitophagy. The results showed that OGD/RP induced autophagy and mitophagy in SH-SY5Y cells. Ru360, the inhibitor of MCU, improved mitochondrial morphology and fuctional stability as well as cell viability, significantly reduced OGD/RP induced mitophagy as evidenced by the decrease in Beclin-1 and the increase in Tom20 and P62 expression. Whereas spermine, the agonist of MCU, had no significant impact on the expression of those mitophagy related proteins compared with OGD/RP group. This study indicates that inhibition of MCU can inhibit excessive mitophagy and protect the neurocytes from I/R injury.

Medienart:

E-Artikel

Erscheinungsjahr:

2016

Erschienen:

2016

Enthalten in:

Zur Gesamtaufnahme - volume:628

Enthalten in:

Neuroscience letters - 628(2016) vom: 15. Aug., Seite 24-9

Sprache:

Englisch

Beteiligte Personen:

Yu, Shoushui [VerfasserIn]
Zheng, Shengfa [VerfasserIn]
Leng, Jing [VerfasserIn]
Wang, Shilei [VerfasserIn]
Zhao, Tao [VerfasserIn]
Liu, Jia [VerfasserIn]

Links:

Volltext

Themen:

2FZ7Y3VOQX
BECN1 protein, human
Beclin-1
Calcium Channels
Ischemia/reperfusion injury
Journal Article
MCU
Membrane Transport Proteins
Mitochondrial Precursor Protein Import Complex Proteins
Mitochondrial calcium uniporter
Mitophagy
Neuroprotection
P62 protein, human
RNA-Binding Proteins
Receptors, Cell Surface
Ru 360
Ruthenium Compounds
Spermine
TOMM20 protein, human

Anmerkungen:

Date Completed 13.06.2017

Date Revised 04.12.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.neulet.2016.06.012

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM261286641