【摘 要】
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Stroke is the fifth leading cause of death for Americans,and about 87%of all strokes are ischemic strokes.Astrogliosis plays a crucial role in the pathophysiology of delayed neuronal death(DND)followi
【机 构】
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Institute of Nervous System Diseases,Xuzhou Medical University,84 West Huai-Hai Road,Xuzhou,221002,J
【出 处】
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第九届海内外华人神经科学家研讨会(The 9th Symposium for Chinese Neuroscientis
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Stroke is the fifth leading cause of death for Americans,and about 87%of all strokes are ischemic strokes.Astrogliosis plays a crucial role in the pathophysiology of delayed neuronal death(DND)following ischemic stroke.Here we reported that astrocyte geranylgeranyltransferase I(GGTI)-mediated Rac1 activation up-regulated NF-κB expression and promoted the neuronal apoptosis after oxygen-glucose deprivation followed by oxygen-glucose regeneration(OGD/R).We found that GGTIβ,a specific subunit of GGTI,and NF-κB-p65 levels as determined by Western blot and/or immunofluorescence were significantly up-regulated in the reactive astrocytes both in rat transient middle cerebral artery occlusion(tMCAO)and in cell OGD/R models.The increased expression of GGTIβ and p65 was associated with the DND in the ischemic brain.Inhibiting astrocyte GGTI activity by its specific inhibitor GGTi-2147 treatment reduced the activity of Rac1(one of substrates for GGTI-mediated prenylation),down-regulated the expression of p65,and ameliorated the OGD/R-induced neuronal apoptosis.Astrocytes transfected with wild type Rac1,but not the unprenylated Rac1,up-regulated the p65 protein levels and promoted the co-cultured neuronal apoptosis.Furthermore,over-expression of unprenylated Rac1 in astrocytes significantly decreased the neuronal apoptosis.In addition,over-expression of NF-κB-p65 in astrocytes significantly increased the co-cultured neuronal apoptosis under OGD/R condition.Our findings suggest that astrocyte GGTI-mediated Rac1 activation contributed to the DND and that GGTIRac1-NF-κB signaling may be a potential target for the therapy of ischemic brain injury.
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