{"title":"蛋白激酶CK2调节链脲佐菌素诱导的糖尿病小鼠结肠血小板衍生生长因子受体α阳性细胞中3型小导钙激活钾通道的钙敏感性","authors":"Ni-Na Song, Xu Huang, Hong-Li Lu, Chen Lu, Jie Chen, Wen-Xie Xu","doi":"10.5056/jnm22052","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/aims: </strong>The gastrointestinal symptom of diabetes mellitus, chronic constipation, seriously affects patients' life. Whereas, the mechanism of chronic constipation is still ambiguous, resulting in a lack of effective therapies for this symptom. As a part of the smooth muscle cells, interstitial cells of Cajal, and platelet-derived growth factor receptor alpha-positive (PDGFRα<sup>+</sup>) cells syncytium (SIP syncytium), PDGFRα<sup>+</sup> cells play an important role in regulating colonic motility. According to our previous study, in PDGFRα<sup>+</sup> cells in colons of diabetic mice, the function of the P2Y1 purinergic receptor/type 3 small-conductance calcium-activated potassium (SK3) channel signaling pathway is strengthened, which may lead to colonic dysmotility. The purpose of this study is to investigate the changes in SK3 channel properties of PDGFRα<sup>+</sup> cells in diabetic mice.</p><p><strong>Methods: </strong>Whole-cell patch clamp, Western blotting, superoxide dismutase activity measurement, and malondialdehyde measurement were main methods in the present study.</p><p><strong>Results: </strong>The present study revealed that when dialysed with low calcium ion (Ca<sup>2+</sup>) solution, the SK3 current density was significantly decreased in PDGFRα<sup>+</sup> cells from diabetic mice. However, the SK3 current density in PDGFRα<sup>+</sup> cells was enhanced from diabetic mice when dialysed with high Ca<sup>2+</sup> solution. Moreover, hydrogen peroxide-treatment mimicked this phenomenon in SK3 transgenic HEK293 cells. The subunit of SK3 channels, protein kinase CK2, was up-regulated in colonic muscle layers and hydrogen peroxide-treated HEK293 cells. Additionally, protein phosphatase 2A, the subunit of SK3 channels, was not changed in streptozotocin-treated mouse colons or hydrogen peroxide-treated HEK293 cells.</p><p><strong>Conclusion: </strong>The diabetic oxidative stress-induced upregulation of CK2 contributed to modulating SK3 channel sensitivity to Ca<sup>2+</sup> in colonic PDGFRα<sup>+</sup> cells, which may result in colonic dysmotility in diabetic mice.</p>","PeriodicalId":16543,"journal":{"name":"Journal of Neurogastroenterology and Motility","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/36/c1/jnm-29-2-250.PMC10083106.pdf","citationCount":"0","resultStr":"{\"title\":\"Protein Kinase CK2 Modulates the Calcium Sensitivity of Type 3 Small-conductance Calcium-activated Potassium Channels in Colonic Platelet-derived Growth Factor Receptor Alpha-positive Cells From Streptozotocin-induced Diabetic Mice.\",\"authors\":\"Ni-Na Song, Xu Huang, Hong-Li Lu, Chen Lu, Jie Chen, Wen-Xie Xu\",\"doi\":\"10.5056/jnm22052\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background/aims: </strong>The gastrointestinal symptom of diabetes mellitus, chronic constipation, seriously affects patients' life. Whereas, the mechanism of chronic constipation is still ambiguous, resulting in a lack of effective therapies for this symptom. As a part of the smooth muscle cells, interstitial cells of Cajal, and platelet-derived growth factor receptor alpha-positive (PDGFRα<sup>+</sup>) cells syncytium (SIP syncytium), PDGFRα<sup>+</sup> cells play an important role in regulating colonic motility. According to our previous study, in PDGFRα<sup>+</sup> cells in colons of diabetic mice, the function of the P2Y1 purinergic receptor/type 3 small-conductance calcium-activated potassium (SK3) channel signaling pathway is strengthened, which may lead to colonic dysmotility. The purpose of this study is to investigate the changes in SK3 channel properties of PDGFRα<sup>+</sup> cells in diabetic mice.</p><p><strong>Methods: </strong>Whole-cell patch clamp, Western blotting, superoxide dismutase activity measurement, and malondialdehyde measurement were main methods in the present study.</p><p><strong>Results: </strong>The present study revealed that when dialysed with low calcium ion (Ca<sup>2+</sup>) solution, the SK3 current density was significantly decreased in PDGFRα<sup>+</sup> cells from diabetic mice. However, the SK3 current density in PDGFRα<sup>+</sup> cells was enhanced from diabetic mice when dialysed with high Ca<sup>2+</sup> solution. Moreover, hydrogen peroxide-treatment mimicked this phenomenon in SK3 transgenic HEK293 cells. The subunit of SK3 channels, protein kinase CK2, was up-regulated in colonic muscle layers and hydrogen peroxide-treated HEK293 cells. Additionally, protein phosphatase 2A, the subunit of SK3 channels, was not changed in streptozotocin-treated mouse colons or hydrogen peroxide-treated HEK293 cells.</p><p><strong>Conclusion: </strong>The diabetic oxidative stress-induced upregulation of CK2 contributed to modulating SK3 channel sensitivity to Ca<sup>2+</sup> in colonic PDGFRα<sup>+</sup> cells, which may result in colonic dysmotility in diabetic mice.</p>\",\"PeriodicalId\":16543,\"journal\":{\"name\":\"Journal of Neurogastroenterology and Motility\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2023-04-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/36/c1/jnm-29-2-250.PMC10083106.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Neurogastroenterology and Motility\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.5056/jnm22052\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neurogastroenterology and Motility","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.5056/jnm22052","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Protein Kinase CK2 Modulates the Calcium Sensitivity of Type 3 Small-conductance Calcium-activated Potassium Channels in Colonic Platelet-derived Growth Factor Receptor Alpha-positive Cells From Streptozotocin-induced Diabetic Mice.
Background/aims: The gastrointestinal symptom of diabetes mellitus, chronic constipation, seriously affects patients' life. Whereas, the mechanism of chronic constipation is still ambiguous, resulting in a lack of effective therapies for this symptom. As a part of the smooth muscle cells, interstitial cells of Cajal, and platelet-derived growth factor receptor alpha-positive (PDGFRα+) cells syncytium (SIP syncytium), PDGFRα+ cells play an important role in regulating colonic motility. According to our previous study, in PDGFRα+ cells in colons of diabetic mice, the function of the P2Y1 purinergic receptor/type 3 small-conductance calcium-activated potassium (SK3) channel signaling pathway is strengthened, which may lead to colonic dysmotility. The purpose of this study is to investigate the changes in SK3 channel properties of PDGFRα+ cells in diabetic mice.
Methods: Whole-cell patch clamp, Western blotting, superoxide dismutase activity measurement, and malondialdehyde measurement were main methods in the present study.
Results: The present study revealed that when dialysed with low calcium ion (Ca2+) solution, the SK3 current density was significantly decreased in PDGFRα+ cells from diabetic mice. However, the SK3 current density in PDGFRα+ cells was enhanced from diabetic mice when dialysed with high Ca2+ solution. Moreover, hydrogen peroxide-treatment mimicked this phenomenon in SK3 transgenic HEK293 cells. The subunit of SK3 channels, protein kinase CK2, was up-regulated in colonic muscle layers and hydrogen peroxide-treated HEK293 cells. Additionally, protein phosphatase 2A, the subunit of SK3 channels, was not changed in streptozotocin-treated mouse colons or hydrogen peroxide-treated HEK293 cells.
Conclusion: The diabetic oxidative stress-induced upregulation of CK2 contributed to modulating SK3 channel sensitivity to Ca2+ in colonic PDGFRα+ cells, which may result in colonic dysmotility in diabetic mice.
期刊介绍:
Journal of Neurogastroenterology and Motility (J Neurogastroenterol Motil) is a joint official journal of the Korean Society of Neurogastroenterology and Motility, the Thai Neurogastroenterology and Motility Society, the Japanese Society of Neurogastroenterology and Motility, the Indian Motility and Functional Disease Association, the Chinese Society of Gastrointestinal Motility, the South East Asia Gastro-Neuro Motility Association, the Taiwan Neurogastroenterology and Motility Society and the Asian Neurogastroenterology and Motility Association, launched in January 2010 after the title change from the Korean Journal of Neurogastroenterology and Motility, published from 1994 to 2009.