Xiaolan Zhang

Sichuan University, Hua-yang, Sichuan, China

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Publications (3)7.39 Total impact

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    ABSTRACT: Hypoxia-inducible factor-1α (HIF-1α) is a key transciptional regulator of cellular and systemic oxygen homeostasis. Previous studies have shown that the regulation of HIF-1α is involved in the activation of PI3K/Akt pathway in some cells. However, whether this pathway plays a role in modulating HIF-1α in cultured cortical neurons during hypoxia-ischemia (HI) remains unclear. We therefore investigated the relationship between phosphoinositid 3-kinase/Akt (PI3K/Akt) pathway and HIF-1α expression in cultured neurons using an oxygen and glucose deprivation (OGD) model. In this study, cortical neurons cultured in vitro were subjected to OGD for 3h followed by reperfusion. The expressions of HIF-1α, VEGF, total Akt and phosphorelated-Akt (p-Akt) were detected by RT-PCR, Western blot and immunocytochemistry. We found that HIF-1α and VEGF were increased at 4h and peaked at 8h after OGD. Meanwhile, p-Akt increased and peaked at 4h after reperfusion, preceding HIF-1α expression. Pretreatment with wortmannin, a PI3K/Akt pathway inhibitor, significantly inhibited p-Akt expression and further attenuated both transcription and translation of HIF-1α and VEGF. Collectively, our findings suggested that PI3K/Akt signaling pathway might be involved in HIF-1α regulation after OGD in cultured cortical neurons.
    Neuroscience Letters 09/2009; 461(1):1-6. DOI:10.1016/j.neulet.2009.03.091 · 2.06 Impact Factor
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    ABSTRACT: The proapoptotic function of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) phosphatase has been linked to its capacity to antagonize the phosphatidylinositol-3-kinase-Akt signaling pathway. Previous studies have shown that the Forkhead transcriptional factor (FOXO3a) is a critical effector of the PTEN-mediated tumor suppressor. However, whether the PTEN-Akt-FOXO3a pathway is involved in neuronal apoptosis in developing rat brain after hypoxia-ischemia (HI) is unclear. In this study, we generated an HI model using postnatal day 10 rats. Immunohistochemistry and western blot were used to detect the expression of total and phosphorylated PTEN, Akt, and FOXO3a, as well as its target gene Bim. We found that dephosphorylation of PTEN was accompanied by dephosphorylation of Akt and FOXO3a, which induced FOXO3a translocation into the nucleus and upregulated the expression of Bim. Furthermore, we found that PTEN inhibition by bisperoxovanadium significantly increased the phosphorylation of Akt and FOXO3a, decreased the nuclear translocation of FOXO3a, and inhibited Bim expression after HI. Moreover, the downregulation of Bim caused by PTEN inhibition attenuated cellular apoptosis in developing rat brain. Our findings suggest that the PTEN-Akt-FOXO3a pathway is involved in neuronal apoptosis in neonatal rat brain after HI. Agents targeting PTEN may offer a promise to rescue neurons from HI brain damage.
    Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 08/2009; 29(12):1903-13. DOI:10.1038/jcbfm.2009.102 · 5.34 Impact Factor
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    ABSTRACT: To explore the change tendency of hypoxia-inducible factor-1alpha (HIF-1alpha) and extracellular signal-regulated kinase 1/2 (ERK1/2) in fetal rat cerebral cortex neurons cultured in vitro after hypoxia-ischemia reperfusion and to investigate their mutual relationship. Cortical neurons obtained from cerebral cortex of 15 pregnant SD rats at 16-18 days of gestation underwent primary culture. The primary neurons 5 days after culture were adopted to establish model of oxygen and glucose deprivation (OGD). The experiment was divided into 4 groups: the experimental group 1, culture medium was changed to neuron complete medium containing glucose after the preparation of OGD model to form reperfusion, and the neurons were observed 0, 2, 4, 8, 12 and 24 hours after reperfusion; the control group 1, the neurons were treated with normal medium; the experimental group 2, the neurons were pretreated with U0126 followed by the preparation of OGD model, and the neurons were observed 4 and 8 hours after reperfusion; the control group 2, the neurons were pretreated with DMSO, and other treatments were the same as the experimental group 2. Expressions of HIF-1alpha, VEGF protein, ERK1/2 and p-ERK1/2 were detected by Western blot. Expression and distribution of p-ERK1/2 and HIF-1alpha protein were detected by SABC immunocytochemistry method. Complicated synaptic connections between cortical neurons processes were observed 5 days after culture. The expression of HIF-1alpha and VEGF were increased gradually, peaked at 8 hours, and decreased gradually after 12 hours in the experimental group 1, and there were significant differences between the experimental group 1 and the control group 1 (P < 0.05). There was no significant difference between the experimental group 1 and the control group 1 in terms of ERK1/2 protein expression (P > 0.05). The p-ERK1/2 protein expression in the experimental group 1 started to increase at 2 hours, peaked at 4 hours, and started to decrease at 8 hours, showing significant differences compared with the control group 1 (P < 0.01). In the experimental group 2, the p-ERK1/2 protein decreased, and HIF-1 and VEGF protein expression subsequently decreased, showing significant differences compared with the control group 2 (P < 0.05). There was no significant difference between the experimental group 2 and the control group 2 in terms of ERK1/2 protein expression at each time point (P > 0.05). Immunocytochemistry staining showed that p-ERK1/2 and HIF-1alpha expression decreased, and the yellow-brown staining of the neurons was reduced. Expressions of HIF-1alpha and its target-gene VEGF protein in the cortex neurons after OGD reperfusion are time-dependent. Their expressions decrease when ERK1/2 signaling pathway is inhibited, indicating the pathway plays an important role in the regulation of HIF-1alpha and VEGF induced by OGD of cortical neurons.
    Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery 08/2009; 23(8):954-8.