[Effect of the NF-κB/iNOS Signaling Pathway on Spiral Ganglion in Mouse Model of Sensorineural Hearing Loss]

Overview

Journal Sichuan Da Xue Xue Bao Yi Xue Ban

Specialty General Medicine

Date 2022 Jul 24

PMID 35871734

Authors

Kai Chen

Rui Zhao

Li Zhou

Li-Li Long

Yue-di Tang

Affiliations

Soon will be listed here.

Abstract

Objective: To explore the effect of changes in the expression level of necorsis factor (NF)-κB/inducible nitric oxide synthase (iNOS) signaling pathway on hearing loss in a mouse model of sensorineural hearing loss (SNHL) induced by 3-nitropropionic acid (3-NP).

Methods: The animal model was established by tympanic injection. C57BL/6 male mice were divided into three groups, 3-NP group receiving tympanic injection of 3-NP solution, 3-NP+EVP4593 group receiving tympanic injection of 3-NP solution and intraperitoneal injection of EVP4593 solution, and a control group receiving tympanic injection of phosphate buffered saline (PBS). Auditory brainstem response (ABR) was tested before and after injection. After 4 weeks, the cochlea was harvested and immunohistochemistry and qRT-PCR of NF-κB p65, RelB, iNOS, and Caspase-3 were conducted accordingly.

Results: The hearing thresholds of the 3-NP group were higher than those of the control group and the 3-NP+EVP4593 group ( <0.05), and the hearing thresholds of the 3-NP+EVP4593 group were also higher than those of the control group ( <0.05). Immunofluorescence staining and qRT-PCR results showed that 3-NP exposure caused an increase in the expressions of NF-κB p65, RelB, and iNOS in the spiral ganglion in comparison with those of the control group ( <0.05), and their expressions decreased with the administration of EVP4593 ( <0.05). The expression of Caspase-3 in the spiral ganglion cells in the 3-NP group was higher than that in the control group, while in the 3-NP+EVP4593 group, it was lower than that in the 3-NP group ( <0.05).

Conclusion: This study found that, by activating the NF-κB/iNOS signaling pathway, 3-NP may cause inflammation in the spiral ganglion of the cochlear in the SNHL model mice, which may play an important role in the pathogenesis of SNHL.

References

Lisakovska O, Shymanskyy I, Mazanova A, Khomenko A, Veliky M . Vitamin D protects against prednisolone-induced liver injury associated with the impairment of the hepatic NF-κB/iNOS/NO pathway. Biochem Cell Biol. 2016; 95(2):213-222. DOI: 10.1139/bcb-2016-0070. View

Sone M, Hayashi H, Yamamoto H, Hoshino T, Mizushima T, Nakashima T . Upregulation of HSP by geranylgeranylacetone protects the cochlear lateral wall from endotoxin-induced inflammation. Hear Res. 2005; 204(1-2):140-6. DOI: 10.1016/j.heares.2005.01.012. View

Gerondakis S, Grumont R, Gugasyan R, Wong L, Isomura I, Ho W . Unravelling the complexities of the NF-kappaB signalling pathway using mouse knockout and transgenic models. Oncogene. 2006; 25(51):6781-99. DOI: 10.1038/sj.onc.1209944. View

Tian C, Kim Y, Kim Y, Park K, Kim S, Kim Y . Korean red ginseng ameliorates acute 3-nitropropionic acid-induced cochlear damage in mice. Neurotoxicology. 2012; 34:42-50. DOI: 10.1016/j.neuro.2012.10.008. View

Vallabhapurapu S, Karin M . Regulation and function of NF-kappaB transcription factors in the immune system. Annu Rev Immunol. 2009; 27:693-733. DOI: 10.1146/annurev.immunol.021908.132641. View

Dohi T, Kawashima R, Kawamura Y, Otsubo T, Hagiwara T, Amatucci A . Pathological activation of canonical nuclear-factor κB by synergy of tumor necrosis factor α and TNF-like weak inducer of apoptosis in mouse acute colitis. Cytokine. 2014; 69(1):14-21. DOI: 10.1016/j.cyto.2014.05.001. View

Baud V, Karin M . Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls. Nat Rev Drug Discov. 2009; 8(1):33-40. PMC: 2729321. DOI: 10.1038/nrd2781. View

Hoffmann A, Baltimore D . Circuitry of nuclear factor kappaB signaling. Immunol Rev. 2006; 210:171-86. DOI: 10.1111/j.0105-2896.2006.00375.x. View

Watanabe K, Inai S, Jinnouchi K, Bada S, Hess A, Michel O . Nuclear-factor kappa B (NF-kappa B)-inducible nitric oxide synthase (iNOS/NOS II) pathway damages the stria vascularis in cisplatin-treated mice. Anticancer Res. 2003; 22(6C):4081-5. View

10.

Hoya N, Okamoto Y, Kamiya K, Fujii M, Matsunaga T . A novel animal model of acute cochlear mitochondrial dysfunction. Neuroreport. 2004; 15(10):1597-600. DOI: 10.1097/01.wnr.0000133226.94662.80. View

11.

Yamamoto H, Omelchenko I, Shi X, Nuttall A . The influence of NF-kappaB signal-transduction pathways on the murine inner ear by acoustic overstimulation. J Neurosci Res. 2009; 87(8):1832-40. PMC: 2811430. DOI: 10.1002/jnr.22018. View

12.

Masuda M, Nagashima R, Kanzaki S, Fujioka M, Ogita K, Ogawa K . Nuclear factor-kappa B nuclear translocation in the cochlea of mice following acoustic overstimulation. Brain Res. 2005; 1068(1):237-47. DOI: 10.1016/j.brainres.2005.11.020. View

13.

Chang M, Rhee J, Kim S, Kim Y . The Protective Effect of Egb 761 Against 3-Nitropropionic Acid-Induced Hearing Loss: The Role of Sirtuin 1. Clin Exp Otorhinolaryngol. 2017; 11(1):9-16. PMC: 5831657. DOI: 10.21053/ceo.2017.00626. View

14.

Conti A, Miscusi M, Cardali S, Germano A, Suzuki H, Cuzzocrea S . Nitric oxide in the injured spinal cord: synthases cross-talk, oxidative stress and inflammation. Brain Res Rev. 2007; 54(1):205-18. DOI: 10.1016/j.brainresrev.2007.01.013. View

15.

Kearns J, Hoffmann A . Integrating computational and biochemical studies to explore mechanisms in NF-{kappa}B signaling. J Biol Chem. 2008; 284(9):5439-43. PMC: 2645808. DOI: 10.1074/jbc.R800008200. View

16.

Yin H, Ma X, Liu F, Xia M, Xu A . Protective effect of geranylgeranylacetone on cisplatin ototoxicity. Chemotherapy. 2008; 55(1):1-5. DOI: 10.1159/000166382. View