Knockdown of sorcin increases HEI-OC1 cell damage induced by cisplatin in vitro

Copyright © 2021. Published by Elsevier Inc..

Hearing loss caused by ototoxic drugs is a kind of acquired hearing loss. Cisplatin is one of the most commonly used drugs and its main action sites are hair cells (HCs). Sorcin is a drug-resistant calcium-binding protein belonging to the small penta-EF-hand protein family. Sorcin is highly expressed in many tissues, including bone, heart, brain, lung, and skin tissues. Single-cell RNA sequencing showed that sorcin was expressed in the outer HCs of mice, but its role remained unknown. We also found that sorcin was highly expressed in the cytoplasm of cochlear HCs and HEI-OC1 cells. After cisplatin injury, the expression of sorcin in HCs and HEI-OC1 cells decreased significantly. SiRNA transfection technology was used to knock down the expression of sorcin. The results showed that the number of apoptotic cells, the expression of cleaved caspased-3, and the expression of Bax increased while the anti-apoptotic factor Bcl-2 decreased in the siRNA-Sorcin + CIS group. The observed increase in apoptosis was related to the increase of reactive oxygen species (ROS) and the destruction of the mitochondrial membrane potential (MMP). Finally, we found that the downregulated sorcin worked by activating the P-ERK1/2 signaling pathway. Overall, this study showed that sorcin can be used as a new target to prevent the ototoxicity of platinum drugs.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:701

Enthalten in:

Archives of biochemistry and biophysics - 701(2021) vom: 15. Apr., Seite 108752

Sprache:

Englisch

Beteiligte Personen:

Wang, Dan [VerfasserIn]
Shi, Suming [VerfasserIn]
Hsieh, Yue-Lin [VerfasserIn]
Wang, Jiali [VerfasserIn]
Wang, Hui [VerfasserIn]
Wang, Wuqing [VerfasserIn]

Links:

Volltext

Themen:

Bax protein, mouse
Bcl-2-Associated X Protein
Calcium-Binding Proteins
Casp3 protein, mouse
Caspase 3
Cisplatin
EC 3.4.22.-
ERK signaling Pathway
Hair cell
Journal Article
Ototoxicity
Q20Q21Q62J
ROS
Research Support, Non-U.S. Gov't
Sri protein, mouse

Anmerkungen:

Date Completed 20.04.2021

Date Revised 20.04.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.abb.2021.108752

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM322330602