Although previous studies have shown the neuroprotective effects of the adenosine triphosphate （ATP）-sensitive potassium （KATP） channel opener against ischemic neuronal damage, little is known about the mechanisms...Although previous studies have shown the neuroprotective effects of the adenosine triphosphate （ATP）-sensitive potassium （KATP） channel opener against ischemic neuronal damage, little is known about the mechanisms involved. Phosphatidylinositol-3 kinase （PI3K）/v-akt murine thy-moma viral oncogene homolog （Akt） and Bcl-2 are thought to be important factors that mediate neuroprotection. The present study investigated the effects of KATP openers on hypoxia-induced PC12 cell apoptosis, as well as mRNA and protein expression of Akt and Bcl-2. Results demon-strated that pretreatment of PC12 cells with pinacidil, a KATP opener, resulted in decreased PC12 cell apoptosis following hypoxia, as detected by Annexin-V fluorescein isothiocyanate/ propidium iodide double staining flow cytometry. In addition, mRNA and protein expression of phosphorylated Akt （p-Akt） and Bcl-2 increased, as detected by immunofluorescence, Western blot analysis, and reverse-transcription polymerase chain reaction. The protective effect of this preconditioning was attenuated by glipizide, a selective KATP blocker. These results demonstrate for the first time that the protective mechanisms of KATP openers on PC12 cell apoptosis following hypoxia could result from activation of the PI3K/Akt signaling pathway, which further activates expression of the downstream Bcl-2 gene.展开更多
基金the Natural Science Foundation of Liaoning Province,No.20052097,2008225010
文摘Although previous studies have shown the neuroprotective effects of the adenosine triphosphate （ATP）-sensitive potassium （KATP） channel opener against ischemic neuronal damage, little is known about the mechanisms involved. Phosphatidylinositol-3 kinase （PI3K）/v-akt murine thy-moma viral oncogene homolog （Akt） and Bcl-2 are thought to be important factors that mediate neuroprotection. The present study investigated the effects of KATP openers on hypoxia-induced PC12 cell apoptosis, as well as mRNA and protein expression of Akt and Bcl-2. Results demon-strated that pretreatment of PC12 cells with pinacidil, a KATP opener, resulted in decreased PC12 cell apoptosis following hypoxia, as detected by Annexin-V fluorescein isothiocyanate/ propidium iodide double staining flow cytometry. In addition, mRNA and protein expression of phosphorylated Akt （p-Akt） and Bcl-2 increased, as detected by immunofluorescence, Western blot analysis, and reverse-transcription polymerase chain reaction. The protective effect of this preconditioning was attenuated by glipizide, a selective KATP blocker. These results demonstrate for the first time that the protective mechanisms of KATP openers on PC12 cell apoptosis following hypoxia could result from activation of the PI3K/Akt signaling pathway, which further activates expression of the downstream Bcl-2 gene.
文摘目的探讨溃疡性结肠炎(UC)血小板中钾通道和NLRP3的表达,以及与UC临床特征的关联分析。方法收集11例正常对照组和17例UC患者临床资料。提取血小板,采用RT-PCR、Western blot法检测Kca3.1、Kv1.3及NLRP3的表达水平。结果与正常对照组相比,UC患者血小板中Kca3.1、Kv1.3及NLRP3 m RNA表达量均明显增加(t=-6.067、-4.991、-18.981,P<0.05),与UC严重程度无明显相关。UC患者血小板中Kca3.1、Kv1.3及NLRP3蛋白表达量均明显高于对照组,差异有统计学意义(t=-9.627、-7.39、-7.821,P<0.05),与UC严重程度无明显相关。UC患者血小板中Kca3.1与NLRP3蛋白表达水平明显相关(r=0.877,P<0.05),Kv1.3与NLRP3蛋白表达水平有一定的相关性,但差异无统计学意义。UC患者血小板中Kca3.1、Kv1.3及NLRP3蛋白表达与患者临床指标红细胞沉降率、C反应蛋白及Mayo评分均不相关。结论 UC患者血小板中NLRP3与钾通道表达增高,两者具有一定相关。
