The Ameliorative Effect of JNK Inhibitor D-JNKI-1 on Neomycin-Induced Apoptosis in HEI-OC1 Cells

Zhao, Jianqing; Líu, Hao; Huang, Zhiwei; Yang, Ruiming; Gong, Liang

doi:10.3389/fnmol.2022.824762

Cited by 5 publications

(5 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, we investigated the factors involved in VC opposed to neomycin-induced HEI-OC1 cell death. Previous studies have shown that JNK was activated by ROS which formed during oxidative stress [ 8 , 27 ], associated with neomycin-induced apoptosis via p38, MAPK, and JNK [ 6 ] activation in hair cells. JNK activation can be inhibited by antioxidants [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Protective Effects of Vitamin C against Neomycin-Induced Apoptosis in HEI-OC1 Auditory Cell

Gong

Chen

et al. 2022

Neural Plasticity

Self Cite

View full text Add to dashboard Cite

Ototoxic hearing loss results from hair cell death via reactive oxygen species (ROS) overproduction and consequent apoptosis. We investigated the effects of vitamin C (VC) on neomycin-induced HEI-OC1 cell damage, as well as the mechanism of inhibition. HEI-OC1 cells were treated with neomycin or with vitamin C (VC). The results indicated that VC had a protective effect on neomycin-induced HEI-OC1 cell death. Mechanistically, VC decreased neomycin-induced ROS generation, suppressed cell death, and increased cell viability. VC inhibited neomycin-induced apoptosis, ameliorated neomycin reduced antiapoptotic Bcl-2 expression, and suppressed neomycin increased expression of proapoptotic Bax, caspase-3 cleavage and caspase-8. TUNEL labeling demonstrated that VC blocked neomycin-induced apoptosis. Further study revealed that the effect of VC on neomycin-induced hair cell death was through interference with JNK activation and p38 phosphorylation. These results indicate that VC via suppressed ROS generation, which inhibited cell death by counteracting apoptotic signaling induced by neomycin in cells. Hence, VC is a potential candidate for protection agent against neomycin-induced HEI-OC1 cell ototoxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

“…ROS triggers various cell death mechanisms that include caspase-dependent or independent apoptosis and necrosis [ 4 , 5 ]. In addition to apoptosis induced by ROS, neomycin reportedly induces hair cell apoptosis via p38, MAPK, and JNK activation, as well [ 6 – 8 ].…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Vitamin C against Neomycin-Induced Apoptosis in HEI-OC1 Auditory Cell

Gong

Chen

et al. 2022

Neural Plasticity

Self Cite

View full text Add to dashboard Cite

show abstract

“…According to our previous aminoglycoside-induced hair cell damage, neomycin significantly stimulated ROS production and activated program cell death in Tg transgenic zebrafish, considered a crucial target mechanism of otoprotective strategies. The ototoxic effects of neomycin have also been reported to involve c-Jun N-terminal kinase (JUN) and caspase-9 signal transduction [ 46 , 47 ]. Results from in vitro model of cochlear organotypic culture revealed that gentamicin dose-dependently induced outer and inner hair cells damage mediated by increasing ROS and reduced mitochondrial bioenergetics, which was attenuated via inhibition of apoptotic pathway [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Cichoric Acid May Play a Role in Protecting Hair Cells from Ototoxic Drugs

Lai

Cheng

et al. 2022

IJMS

View full text Add to dashboard Cite

Ototoxic hearing loss due to antibiotic medication including aminoglycosides and excess free radical production causes irreversible hair cell injury. Cichoric acid, a naturally occurring phenolic acid, has recently been found to exert anti-oxidative and anti-inflammatory properties through its free radical scavenging capacity. The present study aimed to investigate the protective effects of cichoric acid against neomycin-induced ototoxicity using transgenic zebrafish (pvalb3b: TagGFP). Our results indicated that cichoric acid in concentrations up to 5 μM did not affect zebrafish viability during the 2 h treatment period. Therefore, the otoprotective concentration of cichoric acid was identified as 5 μM under 2 h treatment by counting viable hair cells within the neuromasts of the anterior- and posterior-lateral lines in the study. Pretreatment of transgenic zebrafish with 5 μM of cichoric acid for 2 h significantly protected against neomycin-induced hair cell death. Protection mediated by cichoric acid was, however, lost over time. A terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and FM4-64 staining, respectively, provided in situ evidence that cichoric acid ameliorated apoptotic signals and mechanotransduction machinery impairment caused by neomycin. A fish locomotor test (distance move, velocity, and rotation frequency) assessing behavioral alteration after ototoxic damage revealed rescue due to cichoric acid pretreatment before neomycin exposure. These findings suggest that cichoric acid in 5 μM under 2 h treatment has antioxidant effects and can attenuate neomycin-induced hair cell death in neuromasts. Although cichoric acid offered otoprotection, there is only a small difference between pharmacological and toxic concentrations, and hence cichoric acid can be considered a rather prototypical compound for the development of safer otoprotective compounds.

show abstract

“…HEI-OC1 cells (kindly provided by Dr. Federico Kalinec, UCLA) were cultured under permissive conditions (33 °C, 10% CO 2 ) in high-glucose Dulbecco’s Eagle’s medium (DMEM) containing 10% fetal bovine serum (FBS) without antibiotics, as described in previous studies [ 31 , 32 , 33 , 34 ].…”

Section: Methodsmentioning

confidence: 99%

Identification of Target Proteins Involved in Cochlear Hair Cell Progenitor Cytotoxicity following Gentamicin Exposure

Davies

Mittal

et al. 2022

JCM

View full text Add to dashboard Cite

Given the non-labile, terminal differentiation of inner-ear sensory cells, preserving their function is critical since sensory cell damage results in irreversible hearing loss. Gentamicin-induced cytotoxicity is one of the major causes of sensory cell damage and consequent sensorineural hearing loss. However, the precise molecular mechanisms and target proteins involved in ototoxicity are still unknown. The objective of the present study was to identify target proteins involved in gentamicin-induced cytotoxicity to better characterize the molecular pathways involved in sensory cell damage following ototoxic drug administration using House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). We identified several unique proteins involved in gentamicin-induced cytotoxicity, expression of which were further confirmed using confocal microscopy. Further investigation of these pathways can inform the design and discovery of novel treatment modalities to prevent sensory cell damage and preserve their function.

show abstract

The Ameliorative Effect of JNK Inhibitor D-JNKI-1 on Neomycin-Induced Apoptosis in HEI-OC1 Cells

Cited by 5 publications

References 29 publications

Protective Effects of Vitamin C against Neomycin-Induced Apoptosis in HEI-OC1 Auditory Cell

Protective Effects of Vitamin C against Neomycin-Induced Apoptosis in HEI-OC1 Auditory Cell

Cichoric Acid May Play a Role in Protecting Hair Cells from Ototoxic Drugs

Identification of Target Proteins Involved in Cochlear Hair Cell Progenitor Cytotoxicity following Gentamicin Exposure

Contact Info

Product

Resources

About