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Retroviral Expression of Human Arginine Decarboxylase Reduces Oxidative Stress Injury in Mouse Cortical Astrocytes.

Authors
 Samin Hong  ;  Mi Ran Son  ;  Kyungeun Yun  ;  Won Taek Lee  ;  Kyung Ah Park  ;  Jong Eun Lee 
Citation
 BMC NEUROSCIENCE, Vol.15(99) : 1-10, 2014 
Journal Title
 BMC NEUROSCIENCE 
Issue Date
2014
MeSH
Agmatine/metabolism* ; Animals ; Astrocytes/metabolism* ; Carboxy-Lyases/genetics* ; Carboxy-Lyases/metabolism* ; Cell Hypoxia* ; Cell Survival ; Cells, Cultured ; Cerebral Cortex/cytology* ; Cerebral Cortex/physiology ; Genetic Vectors ; Glucose/deficiency* ; Humans ; Intracellular Space/metabolism ; Matrix Metalloproteinases/metabolism ; Mice ; Nitric Oxide Synthase Type II/metabolism ; Oxidative Stress* ; Retroviridae/genetics
Keywords
Agmatine ; Arginine decarboxylase ; Astrocyte ; Neuroprotection ; Oxidative stress
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. CONCLUSION: 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.
Files in This Item:
T201402608.pdf Download
DOI
10.1186/1471-2202-15-99
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Park, Kyung Ah(박경아)
Lee, Won Taek(이원택) ORCID logo https://orcid.org/0000-0001-7348-9562
Lee, Jong Eun(이종은) ORCID logo https://orcid.org/0000-0001-6203-7413
Hong, Sa Min(홍사민)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/99449
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