title: Retroviral expression of human arginine decarboxylase reduces oxidative stress injury in mouse cortical astrocytes.
abstract: BACKGROUND
  In physiologic and pathologic conditions of the central nervous system (CNS), astrocytes are a double-edged sword. They not only support neuronal homeostasis but also contribute to increases in neuronal demise. A large body of experimental evidence has shown that impaired astrocytes play crucial roles in the pathologic process of cerebral ischemia; therefore, astrocytes may represent a breakthrough target for neuroprotective therapeutic strategies. Agmatine, an endogenous polyamine catalyzed from L-arginine by arginine decarboxylase (ADC), is a neuromodulator and it protects neurons/glia against various injuries.
  
  
  RESULTS
  In this investigation, agmatine-producing mouse cortical astrocytes were developed through transduction of the human ADC gene. Cells were exposed to oxygen-glucose deprivation (OGD) and restored to a normoxic glucose-supplied condition. Intracellular levels of agmatine were measured by high performance liquid chromatography. Cell viability was evaluated by Hoechest/propidium iodide nuclear staining and lactate dehydrogenase assay. Expression of inducible nitric oxide synthase (iNOS) and matrix metalloproteinase s (MMPs) were assessed by a reverse transcription polymerase chain reaction, Western immunoblots, and immunofluorescence. We confirmed that ADC gene-expressed astrocytes produce a great amount of agmatine. These cells were highly resistant to not only OGD but also restoration, which mimicked ischemia-reperfusion injury in vivo. The neuroprotective effects of ADC seemed to be related to its ability to attenuate expression of iNOS and MMPs.
  
  
  CONCLUSIONS
  Our findings imply that astrocytes can be reinforced against oxidative stress by endogenous agmatine production through ADC gene transduction. The results of this study provide new insights that may lead to novel therapeutic approaches to reduce cerebral ischemic injuries.
authors.forename: Samin
authors.initials: S
authors.lastname: Hong
authors.forename: Mi Ran
authors.initials: MR
authors.lastname: Son
authors.forename: Kyungeun
authors.initials: K
authors.lastname: Yun
authors.forename: Won Taek
authors.initials: WT
authors.lastname: Lee
authors.forename: Kyung Ah
authors.initials: KA
authors.lastname: Park
authors.affiliation: Brain Korea 21 Project for Medical Science, and Brain Research Institute, Department of Anatomy, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea. jelee@yuhs.ac.
authors.forename: Jong Eun
authors.initials: JE
authors.lastname: Lee
mesh_terms: D000376:Agmatine / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002262:Carboxy-Lyases / Q000235:genetics* / Q000378:metabolism*; D015687:Cell Hypoxia; D002470:Cell Survival; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000502:physiology; D005822:Genetic Vectors; D005947:Glucose / Q000172:deficiency*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress; D012190:Retroviridae / Q000235:genetics
chemical_list: D000376:Agmatine; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D020782:Matrix Metalloproteinases; D002262:Carboxy-Lyases; C019722:arginine decarboxylase; D005947:Glucose