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Connexin 43 Acts as a Proapoptotic Modulator in Cisplatin-Induced Auditory Cell Death

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dc.contributor.authorKim, YJ-
dc.contributor.authorKim, J-
dc.contributor.authorKim, YS-
dc.contributor.authorShin, B-
dc.contributor.authorChoo, OS-
dc.contributor.authorLee, JJ-
dc.contributor.authorChoung, YH-
dc.date.accessioned2018-05-04T00:24:19Z-
dc.date.available2018-05-04T00:24:19Z-
dc.date.issued2016-
dc.identifier.issn1523-0864-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/14837-
dc.description.abstractAIMS: Gap junction coupling is known to play a role in intercellular communication by the Good Samaritan effect or bystander effect. Nonjunctional connexins (Cxs) may also play certain gap junction-independent roles in cell death or survival. The purpose of the present study was to investigate the role of junctional and nonjunctional Cxs in ototoxic drug-induced auditory cell death by focusing on Cx43 in the cochlea. RESULTS: Nonjunctional Cx43 conditions were prepared by low confluence culture (5 x 10(3)/cm(2)) or a trafficking inhibitor, brefeldin A (BFA), in auditory cells, and short lengthened Cx43s with amino-terminal (NT: amino acids 1-256) or carboxy-terminal (CT: amino acids 257-382) were transfected into Cx-deficient HeLa cells to avoid gap junction formation. Knockdown of nonchannel Cx43 (small interfering RNA [siRNA]) inhibited Cis-diamminedichloroplatinum (cisplatin)-induced cell death regardless of gap junction formation: however, a gap junction blocker, 18 alpha-glycyrrhetinic acid (18alpha-GA), showed inhibitory effect only under the junctional condition. BFA did not show any additive influence on the inhibitory effect of siRNA Cx43. Shortened Cx43-transfected HeLa cells also resulted in a significant increase in cell death under cisplatin. In the animal studies with cisplatin-treated rats, hearing thresholds of auditory brainstem response were significantly preserved by a gap junction blocker, carbenoxolone, showing much more preserved stereocilia of hair cells in scanning electron microscopic findings. Innovation and Conclusion: Cx43 plays a proapoptotic role in cisplatin-induced auditory cell death in both junctional and nonjunctional conditions. Targeting the Cx-mediated signaling control may be helpful in designing new therapeutic strategies for drug-induced ototoxicity. Antioxid. Redox Signal. 25, 623-636.-
dc.language.isoen-
dc.subject.MESHAnimals-
dc.subject.MESHAuditory Cortex-
dc.subject.MESHBrefeldin A-
dc.subject.MESHCell Communication-
dc.subject.MESHCell Death-
dc.subject.MESHCisplatin-
dc.subject.MESHConnexin 43-
dc.subject.MESHGap Junctions-
dc.subject.MESHGene Knockdown Techniques-
dc.subject.MESHHumans-
dc.subject.MESHPhosphorylation-
dc.subject.MESHRats-
dc.titleConnexin 43 Acts as a Proapoptotic Modulator in Cisplatin-Induced Auditory Cell Death-
dc.typeArticle-
dc.identifier.pmid27122099-
dc.contributor.affiliatedAuthor김, 연주-
dc.contributor.affiliatedAuthor추, 옥성-
dc.contributor.affiliatedAuthor정, 연훈-
dc.type.localJournal Papers-
dc.identifier.doi10.1089/ars.2015.6412-
dc.citation.titleAntioxidants & redox signaling-
dc.citation.volume25-
dc.citation.number11-
dc.citation.date2016-
dc.citation.startPage623-
dc.citation.endPage636-
dc.identifier.bibliographicCitationAntioxidants & redox signaling, 25(11). : 623-636, 2016-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.identifier.eissn1557-7716-
dc.relation.journalidJ015230864-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Otolaryngology
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