Neuroprotective effects of agmatine on oxygen-glucose deprived primary-cultured astrocytes and nuclear translocation of nuclear factor-kappa B.

Abstract

To better understand the neuroprotective actions of agmatine in ischemic insults, its effects on astrocytes were investigated using an in vitro oxygen-glucose deprivation (OGD) model. After primary culture, cortical astrocytes were moved into a closed anaerobic chamber and incubated in glucose-free culture media. 4 h later, the cells were restored to normoxic conditions and supplied with glucose for 20 h. The ability of agmatine to rescue astrocytes from OGD only and OGD followed by restoration (OGD-R) was assessed. Cell viability was monitored with or without 100 muM agmatine, using the lactate dehydrogenase (LDH) assay and annexin V flow cytometric assay. For morphological analysis, Hoechst 33258 and propidium iodide double nuclear staining was performed. Expression and phosphorylation of nuclear factor-kappa B (NF-kappaB) family proteins were also investigated by immunoblotting. Results showed that astrocytes had decreased viability following OGD and OGD-R and that agmatine treatment increased cell viability and induced NF-kappaB translocation into the nucleus. Finally, our studies revealed that agmatine can rescue astrocytes from death caused by ischemic and/or ischemic-perfusion neuronal injuries in vitro. Our findings provide new insights that may lead to a novel therapeutic strategy to reduce these kinds of neuronal injuries.

• Authors: Won Taek Lee, Samin Hong, Sung Hwan Yoon, Jae Hwan Kim, Kyung Ah Park, Gong Je Seong, Jong Eun Lee
• Journal: Brain research (Brain Res) Vol. 1281 Pg. 64-70 (Jul 24 2009) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 19465011 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Annexin A5
• NF-kappa B
• Neuroprotective Agents
• Propidium
• Agmatine
• L-Lactate Dehydrogenase
• Glucose
• Bisbenzimidazole

Topics

• Active Transport, Cell Nucleus (drug effects)
• Agmatine (pharmacology)
• Animals
• Annexin A5 (metabolism)
• Astrocytes (cytology, drug effects, physiology)
• Bisbenzimidazole
• Blotting, Western
• Cell Hypoxia (drug effects)
• Cell Survival (drug effects)
• Cells, Cultured
• Cerebral Cortex (cytology, drug effects, physiology)
• Flow Cytometry
• Glucose (deficiency, metabolism)
• L-Lactate Dehydrogenase (metabolism)
• Mice
• Mice, Inbred ICR
• NF-kappa B (metabolism)
• Neuroprotective Agents (pharmacology)
• Phosphorylation (drug effects)
• Propidium