title: Decreased Poly(ADP-Ribose) Polymerase 1 Expression Attenuates Glucose Oxidase-Induced Damage in Rat Cochlear Marginal Strial Cells.
abstract: Oxidative damage to the inner ear is responsible for several types of sensorineural deafness. Cochlear stria marginal cells (MCs) are thought to be vulnerable to such oxidative stress. Activated poly(ADP-ribose) polymerase 1 (PARP1) has been implicated in several diseases, but the effect of PARP1 on MCs subjected to oxidative stress remains elusive. In this study, we established an in vitro cellular oxidative stress model using glucose oxidase (GO) and attempted to explore the role that PARP1 plays in the oxidative damage of MCs. In this study, PARP1 and poly-ADP-ribose (PAR) were highly expressed in GO-treated MCs, and this was accompanied by loss of MC viability, excessive generation of reactive oxygen species (ROS), collapse of mitochondria membrane potential (ΔΨm), and redistribution of the mitochondrial downstream pathway-related molecules Bax and cytochrome c, eventually causing MC death. These effects were almost completely counteracted by suppressing PARP1 expression with small interfering RNA (siRNA). We also found that caspase-3 activation was a downstream event of PARP activation and that apoptosis of MCs was suppressed, although not completely, by pretreatment with the pan-caspase inhibitor z-VAD-fmk. The suppression was less than that when PARP1 expression was inhibited. We conclude that GO treatment induces activation of PARP1, which causes MC damage via mitochondrial mediation. PARP1 plays a pivotal role in GO-induced MC death, at least in part, via the caspase-3 cascade. Our study might provide a new cellular and molecular approach for the treatment of oxidative stress-related sensorineural deafness.
authors.affiliation: Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.|Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital, Wuhan University, 238 Jiefang Road, Wuhan, 430060, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.
authors.forename: Wenqi
authors.initials: W
authors.lastname: Zuo
authors.affiliation: Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China. entwjkong@hust.edu.cn.
authors.forename: Weijia
authors.initials: W
authors.lastname: Kong
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003051:Cochlea / Q000201:enzymology* / Q000473:pathology*; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005949:Glucose Oxidase; D042541:Intracellular Space / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D045304:Cytochromes c; D005949:Glucose Oxidase; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases
keywords: Apoptosis; Hearing loss; Marginal cell; Mitochondria; Oxidative stress; Poly(ADP-ribose) polymerase 1