Endoplasmic Reticulum Stress Is Involved in Cochlear Cell Apoptosis in a Cisplatin-Induced Ototoxicity Rat Model

Zong, Shimin; Liu, Tianyi; Wan, Fangmin; Chen, Pei; Luo, Pan; Xiao, Hongjun

doi:10.1159/000480346

Cited by 34 publications

(18 citation statements)

References 37 publications

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“…This study revealed that treatment with cisplatin increased the levels of active caspase-12 in cochlear cells, a finding indicative of cisplatin-induced activation of ER-specific apoptosis. The increased expression of CHOP and cleaved caspase-9 suggested a close relationship between severe ER stress and mitochondria-dependent apoptosis in cochlear cells of cisplatin-treated rats [50].…”

Section: Hearing Lossmentioning

confidence: 89%

Impact of Endoplasmic Reticulum Stress in Otorhinolaryngologic Diseases

Jung

Kim

Yeo

2020

IJMS

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The endoplasmic reticulum (ER) is an important organelle for normal cellular function and homeostasis in most living things. ER stress, which impairs ER function, occurs when the ER is overwhelmed by newly introduced immature proteins or when calcium in the ER is depleted. A number of diseases are associated with ER stress, including otorhinolaryngological diseases. The relationship between ER stress and otorhinolaryngologic conditions has been the subject of investigation over the last decade. Among otologic diseases associated with ER stress are otitis media and hearing loss. In rhinologic diseases, chronic rhinosinusitis, allergic rhinitis, and obstructive sleep apnea are also significantly associated with ER stress. In this review, we provide a comprehensive overview of the relationship between ER stress and otorhinolaryngological diseases, focusing on the current state of knowledge and mechanisms that link ER stress and otorhinolaryngologic diseases.

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Section: Hearing Lossmentioning

confidence: 89%

Impact of Endoplasmic Reticulum Stress in Otorhinolaryngologic Diseases

Jung

Kim

Yeo

2020

IJMS

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“…C/EBP genes are also involved in various biological functions. For example, C/EBPζ is involved in cochlear cell apoptosis in rats [41] and may coregulate the inner ear development with GATA binding protein 2 (GATA2) [42]; Hata et al (2005) reported that C/EBPβ promotes the differentiation of mouse mesenchymal cells into the osteoblast lineage in cooperation with Runt-related transcription factor 2 (Runx2) transcription factor [43]. Allele-speci c induction of Interleukin 1 beta (IL-1b) expression by C/EBPβ contributes to increased tuberculosis susceptibility in humans [44].…”

Section: Discussionmentioning

confidence: 99%

Genome-wide phylogenetic analysis, expression pattern, and transcriptional regulatory network of the pig C/EBP gene family

Zhang

Wang

Liu

et al. 2020

Preprint

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Background: The vertebrate C/EBP transcription factors regulate many important biological processes, such as cell proliferation, differentiation, signal transduction, inflammation, and energy metabolism. The first C/EBP protein was identified in rat liver nuclei. Development of sequencing technology resulted in identification of the C/EBP genes in various species. In this study, a bioinformatics approach was used to determine the distribution of the members of the C/EBP family in vertebrates. A phylogenetic tree was constructed to analyze the C/EBP genes in vertebrates. Based on RNA-seq data, the expression patterns of pig C/EBP members in various tissues were analyzed. In addition, a gene transcription regulatory network was constructed with pig C/EBP members as the core.Results: We identified a total of 92 C/EBP genes in 17 vertebrate genomes. Phylogenetic analysis showed that all C/EBP TFs were classified into two groups; group I contained C/EBPβ TFs, and group II contained the remaining C/EBP TFs. The C/EBPα, C/EBPβ, C/EBPδ, C/EBPγ, and C/EBPζ genes were expressed ubiquitously with inconsistent expression patterns in various tissues. Moreover, a pig C/EBP regulatory network was constructed, including C/EBP genes, TFs, and miRNAs. A total of 39 FFL motifs were detected in the pig C/EBP regulatory network. Based on the RNA-seq data, gene expression patterns related to this FFL sub-network were analyzed in 27 adult Duroc tissues. Certain FFL motifs may be tissue specific. Functional enrichment analysis indicated that C/EBP and its target genes are involved in many important biological pathways. Conclusions: These results provide valuable information that clarifies the evolutionary relationships of the C/EBP family and contributes to the understanding of the biological function of C/EBP genes.

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“…A variety of research has been done for the hearing protection in basic principles and clinical applications. Some reports from the point of cell biology demonstrated that the unfolded protein response (UPR) triggered by endoplasmic reticulum (ER) stress is deeply involved in the pathogenesis of sensorineural hearing loss, inducing apoptosis in cochlear hair cells, stria vascularis and spiral ganglion cells [9,10,11,41,42,43,44]. It has been widely reported that ER stress induces apoptosis, which depends on the activation of the caspase cascade [14,40].…”

Section: Discussionmentioning

confidence: 99%

Caspase-8 Regulates Endoplasmic Reticulum Stress-Induced Necroptosis Independent of the Apoptosis Pathway in Auditory Cells

Kishino

Hayashi

Maeda

et al. 2019

IJMS

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The aim of this study is to elucidate the detailed mechanism of endoplasmic reticulum (ER) stress-induced auditory cell death based on the function of the initiator caspases and molecular complex of necroptosis. Here, we demonstrated that ER stress initiates not only caspase-9-dependent intrinsic apoptosis along with caspase-3, but also receptor-interacting serine/threonine kinase (RIPK)1-dependent necroptosis in auditory cells. We observed the ultrastructural characteristics of both apoptosis and necroptosis in tunicamycin-treated cells under transmission electron microscopy (TEM). We demonstrated that ER stress-induced necroptosis was dependent on the induction of RIPK1, negatively regulated by caspase-8 in auditory cells. Our data suggested that ER stress-induced intrinsic apoptosis depends on the induction of caspase-9 along with caspase-3 in auditory cells. The results of this study reveal that necroptosis could exist for the alternative backup cell death route of apoptosis in auditory cells under ER stress. Interestingly, our data results in a surge in the recognition that therapies aimed at the inner ear protection effect by caspase inhibitors like zVAD-fmk might arrest apoptosis but can also have the unanticipated effect of promoting necroptosis. Thus, RIPK1-dependent necroptosis would be a new therapeutic target for the treatment of sensorineural hearing loss due to ER stress.

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Endoplasmic Reticulum Stress Is Involved in Cochlear Cell Apoptosis in a Cisplatin-Induced Ototoxicity Rat Model

Cited by 34 publications

References 37 publications

Impact of Endoplasmic Reticulum Stress in Otorhinolaryngologic Diseases

Impact of Endoplasmic Reticulum Stress in Otorhinolaryngologic Diseases

Genome-wide phylogenetic analysis, expression pattern, and transcriptional regulatory network of the pig C/EBP gene family

Caspase-8 Regulates Endoplasmic Reticulum Stress-Induced Necroptosis Independent of the Apoptosis Pathway in Auditory Cells

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