title: Neuroprotection of a novel cyclopeptide C*HSDGIC* from the cyclization of PACAP (1-5) in cellular and rodent models of retinal ganglion cell apoptosis.
abstract: OBJECTIVE
  To investigate the protective effects of a novel cyclopeptide C*HSDGIC* (CHC) from the cyclization of Pituitary adenylate cyclase-activating polypeptide (PACAP) (1-5) in cellular and rodent models of retinal ganglion cell apoptosis.
  
  
  RESULTS
  Double-labeling immunohistochemistry was used to detect the expression of Thy-1 and PACAP receptor type 1 in a retinal ganglion cell line RGC-5. The apoptosis of RGC-5 cells was induced by 0.02 J/cm(2) Ultraviolet B irradiation. MTT assay, flow cytometry, fluorescence microscopy were used to investigate the viability, the level of reactive oxygen species (ROS) and apoptosis of RGC-5 cells respectively. CHC attenuated apoptotic cell death induced by Ultraviolet B irradiation and inhibited the excessive generation of ROS. Moreover, CHC treatment resulted in decreased expression of Bax and concomitant increase of Bcl-2, as was revealed by western-blot analysis. The in vivo apoptosis of retinal ganglion cells was induced by injecting 50 mM N-methyl-D-aspartate (NMDA) (100 nmol in a 2 µL saline solution) intravitreally, and different dosages of CHC were administered. At day 7, rats in CHC+ NMDA-treated groups showed obvious aversion to light when compared to NMDA rats. Electroretinogram recordings revealed a marked decrease in the amplitudes of a-wave, b-wave, and photopic negative response due to NMDA damage. In retina receiving intravitreal NMDA and CHC co-treatment, these values were significantly increased. CHC treatment also resulted in less NMDA-induced cell loss and a decrease in the proportion of dUTP end-labeling-positive cells in ganglion cell line.
  
  
  CONCLUSIONS
  C*HSDGIC*, a novel cyclopeptide from PACAP (1-5) attenuates apoptosis in RGC-5 cells and inhibits NMDA-induced retinal neuronal death. The beneficial effects may occur via the mitochondria pathway. PACAP derivatives like CHC may serve as a promising candidate for neuroprotection in glaucoma.
authors.affiliation: Department of Ophthalmology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Bio-engineering Institute of Jinan University, Jinan University, Guangzhou, China.
authors.forename: Rongjie
authors.initials: R
authors.lastname: Yu
authors.affiliation: Department of Ophthalmology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Jiansu
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Parasitology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Chunyun
authors.initials: C
authors.lastname: Wu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003500:Cyclization; D004596:Electroretinography; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D023421:Models, Animal; D008969:Molecular Sequence Data; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000737:chemistry* / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D014466:Ultraviolet Rays; D014785:Vision, Ocular / Q000187:drug effects
chemical_list: D001562:Benzimidazoles; D018696:Neuroprotective Agents; D010456:Peptides, Cyclic; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D017382:Reactive Oxygen Species; D016202:N-Methylaspartate; C017807:bisbenzimide ethoxide trihydrochloride