Protective Effects of Glucose-Related Protein 78 and 94 on Cisplatin-Mediated Ototoxicity

Yi, Junyeong; Kim, Tae Su; Pak, Jhang Ho; Chung, Jong Woo

doi:10.3390/antiox9080686

Cited by 3 publications

(2 citation statements)

References 37 publications

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“…Contrastingly, CHOP was upregulated after cisplatin exposure when Sal strongly decreased the expression. Notably, upregulation of BIP/GRP78 is protective against ischemic injury and also against cisplatin-induced damage in HEI-OC1 cells ( Ouyang et al, 2011 ; López-Hernández et al, 2015 ; Yi et al, 2020 ). Our results supported this point and further showed that pharmacological activation of eIF2α-BIP could alleviate cisplatin-induced ERS and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Salubrinal Protects Against Cisplatin-Induced Cochlear Hair Cell Endoplasmic Reticulum Stress by Regulating Eukaryotic Translation Initiation Factor 2α Signalling

Wen

et al. 2022

Front. Mol. Neurosci.

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ObjectiveCisplatin is a broad-spectrum anti-tumour drug commonly used in clinical practice. However, its ototoxicity greatly limits its clinical application, and no effective method is available to prevent this effect. Endoplasmic reticulum stress (ERS) is reportedly involved in cisplatin ototoxicity, but the exact mechanism remains unclear. Therefore, this study aimed to investigate the role of eukaryotic translation initiation factor 2α (eIF2α) signalling and its dephosphorylation inhibitor salubrinal in cisplatin ototoxicity.MethodsWe evaluated whether salubrinal could protect against cisplatin-induced damage in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and mouse cochlear explants. By knocking down eIF2α, we elucidated the vital role of eIF2α in cisplatin-induced damage in HEI-OC1 cells. Whole-mount immunofluorescent staining and confocal microscopy of mouse cochlear explants and HEI-OC1 cells were performed to analyse cisplatin-induced damage in cochlear hair cells and the auditory cell line.ResultsData suggested salubrinal attenuated cisplatin-induced hair cell injury by inhibiting apoptosis. In addition, salubrinal significantly reduced ERS levels in hair cells via eIF2α signalling, while eIF2α knockdown inhibited the protective effect of salubrinal.SignificanceSalubrinal and eIF2α signalling play a role in protecting against cisplatin-induced ototoxicity, and pharmacological inhibition of eIF2α-mediated ERS is a potential treatment for cisplatin-induced damage in the cochlea and HEI-OC1 cells.

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Section: Discussionmentioning

confidence: 99%

Salubrinal Protects Against Cisplatin-Induced Cochlear Hair Cell Endoplasmic Reticulum Stress by Regulating Eukaryotic Translation Initiation Factor 2α Signalling

Wen

et al. 2022

Front. Mol. Neurosci.

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“…A subsequent study revealed that CoCl 2 pretreatment protected auditory hair cells (HEI-OC1) from H 2 O 2 -mediated cytotoxicity via the activation of the redox-sensitive transcription factors HIF-1α and NRF2, as well as their target gene PRDX6, indicating the protective roles of antioxidant enzymes against noise-triggered oxidative damage [136]. The involvement of oxidative stress in hearing impairment has also been reported in the case of cisplatin-mediated ototoxicity, where mild endoplasmic reticulum (ER)-related stress-induced upregulated expression of glucose-related protein (GRP) 78 and 94, resulting in the attenuation of intracellular ROS accumulation and cisplatin-triggered caspase-associated apoptotic signaling in HEI-OC1 cells [137], as shown in Figure 2.…”

Section: Hypoxic Preconditioningmentioning

confidence: 90%

Antioxidant Therapy against Oxidative Damage of the Inner Ear: Protection and Preconditioning

Pak

Kim

et al. 2020

Antioxidants

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Oxidative stress is an important mechanism underlying cellular damage of the inner ear, resulting in hearing loss. In order to prevent hearing loss, several types of antioxidants have been investigated; several experiments have shown their ability to effectively prevent noise-induced hearing loss, age-related hearing loss, and ototoxicity in animal models. Exogenous antioxidants has been used as single therapeutic agents or in combination. Antioxidant therapy is generally administered before the production of reactive oxygen species. However, post-exposure treatment could also be effective. Preconditioning refers to the phenomenon of pre-inducing a preventative pathway by subtle stimuli that do not cause permanent damage in the inner ear. This renders the inner ear more resistant to actual stimuli that cause permanent hearing damage. The preconditioning mechanism is also related to the induction of antioxidant enzymes. In this review, we discuss the mechanisms underlying antioxidant-associated therapeutic effects and preconditioning in the inner ear.

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Stress-responsive Gdf15 counteracts renointestinal toxicity via autophagic and microbiota reprogramming

et al. 2023

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The integrated stress response (ISR) plays a pivotal role in the cellular stress response, primarily through global translational arrest and the upregulation of cellular adaptation-linked molecules. Growth differentiation factor 15 (Gdf15) is a potent stress-responsive biomarker of clinical inflammatory and metabolic distress in various types of diseases. Herein, we assess whether ISR-driven cellular stress contributes to pathophysiological outcomes by modulating Gdf15. Clinical transcriptome analysis demonstrates that PKR is positively associated with Gdf15 expression in patients with renal injury. Gdf15 expression is dependent on protein kinase R (PKR)-linked ISR during acute renointestinal distress in mice and genetic ablation of Gdf15 aggravates chemical-induced lesions in renal tissues and the gut barrier. An in-depth evaluation of the gut microbiota indicates that Gdf15 is associated with the abundance of mucin metabolism-linked bacteria and their enzymes. Moreover, stress-responsive Gdf15 facilitates mucin production and cellular survival via the reorganization of the autophagy regulatory network. Collectively, ISR-activated Gdf15 counteracts pathological processes via the protective reprogramming of the autophagic network and microbial community, thereby providing robust predictive biomarkers and interventions against renointestinal distress.

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Protective Effects of Glucose-Related Protein 78 and 94 on Cisplatin-Mediated Ototoxicity

Cited by 3 publications

References 37 publications

Salubrinal Protects Against Cisplatin-Induced Cochlear Hair Cell Endoplasmic Reticulum Stress by Regulating Eukaryotic Translation Initiation Factor 2α Signalling

Salubrinal Protects Against Cisplatin-Induced Cochlear Hair Cell Endoplasmic Reticulum Stress by Regulating Eukaryotic Translation Initiation Factor 2α Signalling

Antioxidant Therapy against Oxidative Damage of the Inner Ear: Protection and Preconditioning

Stress-responsive Gdf15 counteracts renointestinal toxicity via autophagic and microbiota reprogramming

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