Retroviral expression of human arginine decarboxylase reduces oxidative stress injury in mouse cortical astrocytes

BMC Neuroscience

Jong Eun Lee²  Kyung Ah Park²  Won Taek Lee²  Kyungeun Yun²  Mi Ran Son²  Samin Hong¹ 

[1] Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Republic of Korea;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

关键词: Oxidative stress;    Neuroprotection;    Astrocyte;    Arginine decarboxylase;    Agmatine;   

Others  :  1091331
DOI  :  10.1186/1471-2202-15-99

 received in 2014-03-26, accepted in 2014-08-20,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Hong et al.; licensee BioMed Central Ltd.

【 图 表 】

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