Protective Effects of Glucose-Related Protein 78 and 94 on Cisplatin-Mediated Ototoxicity
Cisplatin is a widely used chemotherapeutic drug for treating various solid tumors. Ototoxicity is a major dose-limiting side effect of cisplatin, which causes progressive and irreversible sensorineural hearing loss. Here, we examined the protective effects of glucose-related protein (GRP) 78 and 94...
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MDPI AG
2020-08-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/8/686 |
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| author | Junyeong Yi Tae Su Kim Jhang Ho Pak Jong Woo Chung |
| author_facet | Junyeong Yi Tae Su Kim Jhang Ho Pak Jong Woo Chung |
| author_sort | Junyeong Yi |
| collection | DOAJ |
| description | Cisplatin is a widely used chemotherapeutic drug for treating various solid tumors. Ototoxicity is a major dose-limiting side effect of cisplatin, which causes progressive and irreversible sensorineural hearing loss. Here, we examined the protective effects of glucose-related protein (GRP) 78 and 94, also identified as endoplasmic reticulum (ER) chaperone proteins, on cisplatin-induced ototoxicity. Treating murine auditory cells (HEI-OC1) with 25 μM cisplatin for 24 h increased cell death resulting from excessive intracellular reactive oxygen species (ROS) accumulation and caspase-involved apoptotic signaling pathway activation with subsequent DNA fragmentation. GRP78 and GRP94 expression was increased in cells treated with 3 nM thapsigargin or 0.1 μg/mL tunicamycin for 24 h, referred to as mild ER stress condition. This condition, prior to cisplatin exposure, attenuated cisplatin-induced ototoxicity. The involvement of GRP78 and GRP94 induction was demonstrated by the knockdown of GRP78 or GRP94 expression using small interfering RNAs, which abolished the protective effect of mild ER stress condition on cisplatin-induced cytotoxicity. These results indicated that GRP78 and GRP94 induction plays a protective role in remediating cisplatin-ototoxicity. |
| first_indexed | 2024-03-10T18:01:39Z |
| format | Article |
| id | doaj.art-e1fa04773c354635ac35363883bb8c32 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T18:01:39Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
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| series | Antioxidants |
| spelling | doaj.art-e1fa04773c354635ac35363883bb8c322023-11-20T08:51:00ZengMDPI AGAntioxidants2076-39212020-08-019868610.3390/antiox9080686Protective Effects of Glucose-Related Protein 78 and 94 on Cisplatin-Mediated OtotoxicityJunyeong Yi0Tae Su Kim1Jhang Ho Pak2Jong Woo Chung3Department of Otorhinolaryngology-Head and Neck Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-Gu, Seoul 05505, KoreaDepartment of Otorhinolaryngology, School of Medicine, Kangwon National University, Gangwondaehakgil, Chuncheon, Gangwon-Do 24341, KoreaDepartment of Convergence Medicine, University of Ulsan College of Medicine and Asan Institute for Life Sciences, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-Gu, Seoul 05505, KoreaDepartment of Otorhinolaryngology-Head and Neck Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-Gu, Seoul 05505, KoreaCisplatin is a widely used chemotherapeutic drug for treating various solid tumors. Ototoxicity is a major dose-limiting side effect of cisplatin, which causes progressive and irreversible sensorineural hearing loss. Here, we examined the protective effects of glucose-related protein (GRP) 78 and 94, also identified as endoplasmic reticulum (ER) chaperone proteins, on cisplatin-induced ototoxicity. Treating murine auditory cells (HEI-OC1) with 25 μM cisplatin for 24 h increased cell death resulting from excessive intracellular reactive oxygen species (ROS) accumulation and caspase-involved apoptotic signaling pathway activation with subsequent DNA fragmentation. GRP78 and GRP94 expression was increased in cells treated with 3 nM thapsigargin or 0.1 μg/mL tunicamycin for 24 h, referred to as mild ER stress condition. This condition, prior to cisplatin exposure, attenuated cisplatin-induced ototoxicity. The involvement of GRP78 and GRP94 induction was demonstrated by the knockdown of GRP78 or GRP94 expression using small interfering RNAs, which abolished the protective effect of mild ER stress condition on cisplatin-induced cytotoxicity. These results indicated that GRP78 and GRP94 induction plays a protective role in remediating cisplatin-ototoxicity.https://www.mdpi.com/2076-3921/9/8/686cisplatinototoxicitymild ER stress conditionGRP78GRP94auditory cells |
| spellingShingle | Junyeong Yi Tae Su Kim Jhang Ho Pak Jong Woo Chung Protective Effects of Glucose-Related Protein 78 and 94 on Cisplatin-Mediated Ototoxicity Antioxidants cisplatin ototoxicity mild ER stress condition GRP78 GRP94 auditory cells |
| title | Protective Effects of Glucose-Related Protein 78 and 94 on Cisplatin-Mediated Ototoxicity |
| title_full | Protective Effects of Glucose-Related Protein 78 and 94 on Cisplatin-Mediated Ototoxicity |
| title_fullStr | Protective Effects of Glucose-Related Protein 78 and 94 on Cisplatin-Mediated Ototoxicity |
| title_full_unstemmed | Protective Effects of Glucose-Related Protein 78 and 94 on Cisplatin-Mediated Ototoxicity |
| title_short | Protective Effects of Glucose-Related Protein 78 and 94 on Cisplatin-Mediated Ototoxicity |
| title_sort | protective effects of glucose related protein 78 and 94 on cisplatin mediated ototoxicity |
| topic | cisplatin ototoxicity mild ER stress condition GRP78 GRP94 auditory cells |
| url | https://www.mdpi.com/2076-3921/9/8/686 |
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