title: Effect of hypoxia mimetic cobalt chloride on the expression of extracellular-superoxide dismutase in retinal pericytes.
abstract: The initial clinical stage of diabetic retinopathy (DR) is characterized by the development of intraretinal microvascular abnormalities. The increased formation of reactive oxygen species (ROS) is thought to be a key event in the pathogenesis of DR. Extracellular-superoxide dismutase (EC-SOD) is an anti-inflammatory enzyme that is distributed mainly in vascular cells and protects cells from ROS by scavenging superoxide anion. Treatment with cobalt chloride (CoCl(2)) decreased the expression of EC-SOD but not other SOD isozymes in pericytes accompanied with an increase of intracellular ROS production. Pre-treatment with N-acetylcysteine (NAC) significantly suppressed the ROS production and down-regulation of EC-SOD. We observed the activation of caspase-3 and DNA fragmentation as signs of apoptotic process by CoCl(2) treatment. In addition, these phenomena were significantly inhibited by pre-treatment with NAC. EC-SOD enhancer 4-phenyl butyric acid also suppressed the caspase-3 activation. It is known that the presence of a high level of EC-SOD throughout the vessel walls might have an important protective role against superoxide in the vascular system. The decrease in EC-SOD expression accompanied with elevation of ROS level in pericytes under hypoxia might induce and/or promote the ROS-triggered apoptosis of pericytes and the development of pathogenesis in DR.
authors.affiliation: Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Japan. adachi@gifu-pu.ac.jp
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Adachi
authors.forename: Kazunari
authors.initials: K
authors.lastname: Aida
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nishihara
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kamiya
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hara
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020148:Butyric Acid / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D003035:Cobalt / Q000494:pharmacology*; D053938:DNA Fragmentation; D003930:Diabetic Retinopathy / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D015536:Down-Regulation; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D000860:Hypoxia / Q000150:complications* / Q000378:metabolism; D020286:Pericytes / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D020148:Butyric Acid; D003035:Cobalt; D013482:Superoxide Dismutase; D053148:Caspase 3; C018021:cobaltous chloride; D000111:Acetylcysteine