Nimodipine Treatment Protects Auditory Hair Cells from Cisplatin-Induced Cell Death Accompanied by Upregulation of LMO4.
LMO4
Stat3
auditory hair cells
cisplatin
hearing
nimodipine
otoprotection
ototoxicity
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
21 May 2022
21 May 2022
Historique:
received:
12
04
2022
revised:
17
05
2022
accepted:
19
05
2022
entrez:
28
5
2022
pubmed:
29
5
2022
medline:
1
6
2022
Statut:
epublish
Résumé
Ototoxicity is one of the main dose-limiting side effects of cisplatin chemotherapy and impairs the quality of life of tumor patients dramatically. Since there is currently no established standard therapy targeting hearing loss in cisplatin treatment, the aim of this study was to investigate the effect of nimodipine and its role in cell survival in cisplatin-associated hearing cell damage. To determine the cytotoxic effect, the cell death rate was measured using undifferentiated and differentiated UB/OC-1 and UB/OC-2 cells, after nimodipine pre-treatment and stress induction by cisplatin. Furthermore, immunoblot analysis and intracellular calcium measurement were performed to investigate anti-apoptotic signaling, which was associated with a reduced cytotoxic effect after nimodipine pre-treatment. Cisplatin's cytotoxic effect was significantly attenuated by nimodipine up to 61%. In addition, nimodipine pre-treatment counteracted the reduction in LIM Domain Only 4 (LMO4) by cisplatin, which was associated with increased activation of Ak strain transforming/protein kinase B (Akt), cAMP response element-binding protein (CREB), and signal transducers and activators of transcription 3 (Stat3). Thus, nimodipine presents a potentially well-tolerated substance against the ototoxicity of cisplatin, which could result in a significant improvement in patients' quality of life.
Identifiants
pubmed: 35628594
pii: ijms23105780
doi: 10.3390/ijms23105780
pmc: PMC9145067
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Antineoplastic Agents
0
LIM Domain Proteins
0
LMO4 protein, human
0
Nimodipine
57WA9QZ5WH
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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