title: Recombinant protein transduction domain-Cu/Zn superoxide dismutase alleviates bone cancer pain via peroxiredoxin 4 modulation and antioxidation.
abstract: Bone cancer pain (BCP) is a serious chronic clinical condition and reactive oxygen species (ROS) were considered to be involved in its development and persistency. Normally, superoxide dismutase (SOD) converts superoxide anions to hydrogen peroxide (H2O2) and H2O2is then naturalized to be water by peroxiredoxin 4. We reported previously that recombinant protein transduction domain (PTD)-Cu/Zn SOD effectively scavenged excessive ROS and prevented cardiomyocytes from hypoxia-reoxygenation damage. However, whether PTD-Cu/Zn SOD would prevent BCP development is unknown. In the current study, we found that an implanted carcinoma in the rat tibia induced remarkable hyperalgesia, increased H2O2levels and decreased SOD and peroxiredoxin 4 levels. After administration of recombinant PTD-Cu/Zn SOD to these tumor-burden rats, their hyperalgesia was significantly attenuated and peroxiredoxin 4 expression was significantly increased. In addition, an increased expression of N-methyl-d-aspartic acid (NMDA) receptors and a decreased expression of γ-aminobutyric acid (GABA) receptors in this cancer pain were prevented by PTD-Cu/Zn SOD administration or peroxiredoxin 4 overexpression. Our data suggested that reactive oxygen species, at least in part, play a role in cancer metastatic pain development and persistency which can be attenuated by the adminstration of recombinant PTD-Cu/Zn SOD via the peroxiredoxin 4 modulation from oxidative stress.
authors.affiliation: Institute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
authors.forename: Wanjun
authors.initials: W
authors.lastname: Yao
authors.affiliation: Institute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
authors.forename: Haiwen
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Institute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Ruoshi
authors.initials: R
authors.lastname: Shi
authors.affiliation: Institute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China. Electronic address: changbinke-iap@taihehospital.com.
authors.forename: Changbin
authors.initials: C
authors.lastname: Ke
authors.affiliation: Institute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China. Electronic address: Liu6119@163.com.
authors.forename: Juying
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001859:Bone Neoplasms / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D000072716:Cancer Pain / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D018384:Oxidative Stress / Q000187:drug effects; D054464:Peroxiredoxins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000235:genetics; D000072105:Superoxide Dismutase-1 / Q000008:administration & dosage* / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; C557704:PTD4-apoptin protein; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D054464:Peroxiredoxins; C515982:Prdx4 protein, rat; D000072105:Superoxide Dismutase-1
keywords: Bone cancer pain; Oxidative stress; PTD-Cu/Zn SOD; Peroxiredoxin 4