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1.
Anatomy & Cell Biology ; : 325-331, 2010.
Artigo em Inglês | WPRIM | ID: wpr-93237

RESUMO

Minocycline, a tetracycline antibiotic, is now known to protect cells via an anti-inflammatory mechanism. We further explored this effect using an in vitro model of ischemia-like injury to neurons. Coculturing neurons with microglia, the brain's resident immune cell, modestly increased cell death due to oxygen and glucose deprivation (OGD), compared to neurons alone. Treatment of cocultures with minocycline decreased cell death to a level significantly lower than that of neurons alone. Treatment of cocultures with minocycline or inhibitors of various immune mediators, also led to decreased cell death. Importantly, treatment of neuron cultures without added microglia with these same inhibitors of tissue plasminogen activator, matrix metalloproteinases, TNF-alpha and inducible nitric oxide synthase as well as minocycline also led to decreased cell death. Thus, anti-inflammatory treatments appear to be directly protective of neurons from in vitro ischemia.


Assuntos
Morte Celular , Técnicas de Cocultura , Glucose , Isquemia , Metaloproteinases da Matriz , Microglia , Minociclina , Neurônios , Óxido Nítrico Sintase Tipo II , Oxigênio , Tetraciclina , Ativador de Plasminogênio Tecidual , Fator de Necrose Tumoral alfa
2.
Yonsei Medical Journal ; : 471-479, 2001.
Artigo em Inglês | WPRIM | ID: wpr-189145

RESUMO

Hydrogen peroxide is considered to be a dose- and time-dependent mediator in apoptotic and necrotic death. In this study, we examined the signaling of the E6 and E7 proteins with respect to apoptosis or necrosis after H2O2 injury using an in vitro model with overexpressed E6 or E7 genes. For this purpose, the E6 and E7 gene expressing astrocytes were exposed to 0.01 mM and 0.2 mM H2 O2 solutions. Twenty- four hours after treatment with the lower dosage(0.01 mM H2O2), control, E6-expressing cells suffered about 45% injury and LXSN-expressi ng cells decreased by 67% as assessed by LDH release. However, E7-expressing cells showed less injury, resulting in 20-30% of LDH release. Astrocytes expressing E6, E7, LXSN and mock-infected cells showed a typical apoptotic death patter n on the DNA gel after treatment with a low-dose of H2O2 (0.01 mM), however the y died from necrotic death after a high-dose (0.2 mM) H2O2. Overexpression of HPV-E7 genes protected the cells from apoptotic death after a low-dose of H2O2 and from necrotic death after a high-dose of H2O2, while the overexpression of E 6 genes from the necrotic death. E7 expressing astrocytes showed higher catalas e activity and the levels of E2F protein surged more than 100-folds compared with the control astrocytes. We believe that the activity of E7 protein to protect astrocytes from H2O2 injury was at least partly due to increased catalase, a scavenger protein.


Assuntos
Camundongos , Animais , Apoptose/fisiologia , Astrócitos/efeitos dos fármacos , Células Cultivadas , Peróxido de Hidrogênio/farmacologia , Necrose , Proteínas Oncogênicas Virais/genética , Oxidantes/farmacologia , Transdução de Sinais/fisiologia
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