{"title":"Rotigaptide inhibits spontaneous contractions of gastric smooth muscle in diabetic rats via the PKCα-Cx43 pathway","authors":"Lu Changri, Haibei Sun, Yitegele Bao, Mohan Zhang","doi":"10.1002/cbin.12253","DOIUrl":null,"url":null,"abstract":"<p>The study aimed to investigate the effect of rotigaptide (ZP123) on spontaneous contractions of gastric smooth muscle in diabetic rats and explore the underlying mechanisms. Twelve rats were randomly divided into model and normal control groups. Changes in gastric smooth muscle spontaneous contractions in each group were observed. Western blot analysis was performed to detect Cx43 and PKCα expression. Rat gastric smooth muscle cells were cultured in vitro and divided into normal glucose, high glucose and high glucose+rotigaptide group. The intracellular Ca<sup>2+</sup> content was observed by immunofluorescence. The amplitude and frequency of gastric smooth muscle spontaneous contractions were reduced in the model group than the normal control group (all <i>p</i> < .01), which were reduced after rotigatide treatment than before treatment in the model group (all <i>p</i> < .01). The model+rotigaptide group showed decreased membrane expression of Cx43, increased cytoplasmic expression of Cx43, increased membrane expression of p-PKCα Thr<sup>497</sup> and lower membrane/cytoplasm ratio of Cx43 expression compared with the model group (all <i>p</i> < .01). The intracellular Ca<sup>2+</sup> content was increased in the high glucose group than the normal glucose group (<i>p</i> < .01), while no significant difference was observed between the high glucose+rotigaptide and high glucose groups. Our findings suggest that rotigatide can stabilize the intracellular Ca<sup>2+</sup> concentration in gastric smooth muscle cells under high glucose condition by upregulating PKCα activity and downregulating the number of GJs and the opening rate of GJ hemichannels through the PKCα-Cx43 pathway, thus inhibiting spontaneous contractions of gastric smooth muscle in diabetic rats.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"49 1","pages":"92-100"},"PeriodicalIF":3.3000,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Biology International","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cbin.12253","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
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Abstract
The study aimed to investigate the effect of rotigaptide (ZP123) on spontaneous contractions of gastric smooth muscle in diabetic rats and explore the underlying mechanisms. Twelve rats were randomly divided into model and normal control groups. Changes in gastric smooth muscle spontaneous contractions in each group were observed. Western blot analysis was performed to detect Cx43 and PKCα expression. Rat gastric smooth muscle cells were cultured in vitro and divided into normal glucose, high glucose and high glucose+rotigaptide group. The intracellular Ca2+ content was observed by immunofluorescence. The amplitude and frequency of gastric smooth muscle spontaneous contractions were reduced in the model group than the normal control group (all p < .01), which were reduced after rotigatide treatment than before treatment in the model group (all p < .01). The model+rotigaptide group showed decreased membrane expression of Cx43, increased cytoplasmic expression of Cx43, increased membrane expression of p-PKCα Thr497 and lower membrane/cytoplasm ratio of Cx43 expression compared with the model group (all p < .01). The intracellular Ca2+ content was increased in the high glucose group than the normal glucose group (p < .01), while no significant difference was observed between the high glucose+rotigaptide and high glucose groups. Our findings suggest that rotigatide can stabilize the intracellular Ca2+ concentration in gastric smooth muscle cells under high glucose condition by upregulating PKCα activity and downregulating the number of GJs and the opening rate of GJ hemichannels through the PKCα-Cx43 pathway, thus inhibiting spontaneous contractions of gastric smooth muscle in diabetic rats.
期刊介绍：
Each month, the journal publishes easy-to-assimilate, up-to-the minute reports of experimental findings by researchers using a wide range of the latest techniques. Promoting the aims of cell biologists worldwide, papers reporting on structure and function - especially where they relate to the physiology of the whole cell - are strongly encouraged. Molecular biology is welcome, as long as articles report findings that are seen in the wider context of cell biology. In covering all areas of the cell, the journal is both appealing and accessible to a broad audience. Authors whose papers do not appeal to cell biologists in general because their topic is too specialized (e.g. infectious microbes, protozoology) are recommended to send them to more relevant journals. Papers reporting whole animal studies or work more suited to a medical journal, e.g. histopathological studies or clinical immunology, are unlikely to be accepted, unless they are fully focused on some important cellular aspect.
These last remarks extend particularly to papers on cancer. Unless firmly based on some deeper cellular or molecular biological principle, papers that are highly specialized in this field, with limited appeal to cell biologists at large, should be directed towards journals devoted to cancer, there being very many from which to choose.
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