{"title":"三胸蛋白MLL-1在调节神经元离子通道中的差异作用","authors":"Dave Sonya, Z. An","doi":"10.29328/journal.jnnd.1001057","DOIUrl":null,"url":null,"abstract":"Repressive regulation of potassium channel genes by Polycomb group (PcG) proteins contributes to PcG protein-mediated neuroprotection against neuronal ischemic injury, as seen in an ischemic stroke. Here we asked the question whether Trithorax group (TrxG) proteins, the antagonistic partners of PcG proteins (i.e, epigenetic activators targeting the same genes) may also regulate potassium channels. Results of patch-clamp studies on cultured neuronal cells showed that inhibition of TrxG protein MLL-1 led to an increase in potassium channel activity, an unexpected effect for a presumed gene activator. In contrast, decreased sodium currents were observed with MLL-1 inhibition. Increased or decreased levels of potassium channel protein Kv2.1 or sodium channel protein Nav1.2, respectively, were seen with MLL-1 inhibition, as determined by immunocytochemistry. These results, for the first time, demonstrate an involvement of TrxG protein MLL-1 in regulating neuronal ion channels, potentially repressing potassium channel genes.","PeriodicalId":382788,"journal":{"name":"Journal of Neuroscience and Neurological Disorders","volume":"65 1","pages":"0"},"PeriodicalIF":0.0000,"publicationDate":"2021-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Differential roles of trithorax protein MLL-1 in regulating neuronal Ion channels\",\"authors\":\"Dave Sonya, Z. An\",\"doi\":\"10.29328/journal.jnnd.1001057\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Repressive regulation of potassium channel genes by Polycomb group (PcG) proteins contributes to PcG protein-mediated neuroprotection against neuronal ischemic injury, as seen in an ischemic stroke. Here we asked the question whether Trithorax group (TrxG) proteins, the antagonistic partners of PcG proteins (i.e, epigenetic activators targeting the same genes) may also regulate potassium channels. Results of patch-clamp studies on cultured neuronal cells showed that inhibition of TrxG protein MLL-1 led to an increase in potassium channel activity, an unexpected effect for a presumed gene activator. In contrast, decreased sodium currents were observed with MLL-1 inhibition. Increased or decreased levels of potassium channel protein Kv2.1 or sodium channel protein Nav1.2, respectively, were seen with MLL-1 inhibition, as determined by immunocytochemistry. These results, for the first time, demonstrate an involvement of TrxG protein MLL-1 in regulating neuronal ion channels, potentially repressing potassium channel genes.\",\"PeriodicalId\":382788,\"journal\":{\"name\":\"Journal of Neuroscience and Neurological Disorders\",\"volume\":\"65 1\",\"pages\":\"0\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2021-09-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Neuroscience and Neurological Disorders\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.29328/journal.jnnd.1001057\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neuroscience and Neurological Disorders","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.29328/journal.jnnd.1001057","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
在缺血性中风中,Polycomb group (PcG)蛋白对钾通道基因的抑制调控有助于PcG蛋白介导的神经保护,防止神经元缺血性损伤。在这里,我们提出了Trithorax group (TrxG)蛋白,PcG蛋白的拮抗伙伴(即针对相同基因的表观遗传激活因子)是否也可能调节钾通道的问题。膜片钳对培养的神经细胞的研究结果表明,抑制TrxG蛋白MLL-1导致钾通道活性增加,这是一种意想不到的基因激活剂。相比之下,MLL-1抑制可降低钠电流。通过免疫细胞化学测定,MLL-1抑制分别导致钾通道蛋白Kv2.1或钠通道蛋白Nav1.2水平升高或降低。这些结果首次证明了TrxG蛋白MLL-1参与调节神经元离子通道,潜在地抑制钾通道基因。
Differential roles of trithorax protein MLL-1 in regulating neuronal Ion channels
Repressive regulation of potassium channel genes by Polycomb group (PcG) proteins contributes to PcG protein-mediated neuroprotection against neuronal ischemic injury, as seen in an ischemic stroke. Here we asked the question whether Trithorax group (TrxG) proteins, the antagonistic partners of PcG proteins (i.e, epigenetic activators targeting the same genes) may also regulate potassium channels. Results of patch-clamp studies on cultured neuronal cells showed that inhibition of TrxG protein MLL-1 led to an increase in potassium channel activity, an unexpected effect for a presumed gene activator. In contrast, decreased sodium currents were observed with MLL-1 inhibition. Increased or decreased levels of potassium channel protein Kv2.1 or sodium channel protein Nav1.2, respectively, were seen with MLL-1 inhibition, as determined by immunocytochemistry. These results, for the first time, demonstrate an involvement of TrxG protein MLL-1 in regulating neuronal ion channels, potentially repressing potassium channel genes.