Chanting He , Jingjing Jia , Yang Lei , Qian Hu , Yulu Xin , Yafen Chu , Congying Liu , Qiao Niu
{"title":"miR-665 靶向 GNB3 在铝诱导神经细胞凋亡中的作用机制","authors":"Chanting He , Jingjing Jia , Yang Lei , Qian Hu , Yulu Xin , Yafen Chu , Congying Liu , Qiao Niu","doi":"10.1016/j.jtemb.2024.127488","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Aluminum exerts neurotoxic effects through various mechanisms, mainly manifested as impaired learning and memory function.</p></div><div><h3>Methods</h3><p>Forty SD rats were divided into 0, 10, 20, and 40 mM maltol aluminum [Al(mal)<sub>3</sub>] groups. Cell experiments are divided into 0, 100, 200, and 400 μM Al(mal)<sub>3</sub> dose group and control, Al(mal)<sub>3</sub>, Al(mal)<sub>3</sub>+inhibitor NC, Al(mal)<sub>3</sub>+miR-665 inhibitor intervention group. Water maze was used to detect the learning and memory function of rats, HE staining was used to observe the morphology and number of neurons in the CA1 area of the rat hippocampus, Flow cytometry was used to detect the apoptosis of PC12 cells, PCR and Western blotting were used to detect the expression of Caspase3, miR-665 and GNB3/PI3K/AKT proteins. The target binding relationship between miR-665 and GNB3 was verified by double luciferase reporter gene experiment.</p></div><div><h3>Results</h3><p>In vivo experimental results showed that with the increase of Al(mal)<sub>3</sub> concentration, the escape latency of rats was prolonged, the target quadrant dwell time was shortened, and the number of crossing platform was reduced. Moreover, the arrangement of neurons was loose and the number decreased; the expression of Caspase3 and miR-665 increased, while the expression of GNB3/PI3K/AKT proteins decreased. In vitro experiments, with the increase of Al(mal)<sub>3</sub> concentration, apoptosis rate of PC12 cells increased, the expression of Caspase3, miR-665 and GNB3/PI3K/AKT proteins were consistent with rat results. After inhibiting miR-665 in the intervention group experiment, apoptosis rate of PC12 cells in the aluminum exposure group decreased, the expression of Caspase3 and miR-665 decreased, and the expression of GNB3/PI3K/AKT proteins increased.</p></div><div><h3>Conclusion</h3><p>MiR-665 plays an important role in aluminum induced neuronal apoptosis by targeting GNB3 and regulating the PI3K/AKT pathway.</p></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"85 ","pages":"Article 127488"},"PeriodicalIF":3.6000,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The mechanism of miR-665 targeting GNB3 in aluminum-induced neuronal apoptosis\",\"authors\":\"Chanting He , Jingjing Jia , Yang Lei , Qian Hu , Yulu Xin , Yafen Chu , Congying Liu , Qiao Niu\",\"doi\":\"10.1016/j.jtemb.2024.127488\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Aluminum exerts neurotoxic effects through various mechanisms, mainly manifested as impaired learning and memory function.</p></div><div><h3>Methods</h3><p>Forty SD rats were divided into 0, 10, 20, and 40 mM maltol aluminum [Al(mal)<sub>3</sub>] groups. Cell experiments are divided into 0, 100, 200, and 400 μM Al(mal)<sub>3</sub> dose group and control, Al(mal)<sub>3</sub>, Al(mal)<sub>3</sub>+inhibitor NC, Al(mal)<sub>3</sub>+miR-665 inhibitor intervention group. Water maze was used to detect the learning and memory function of rats, HE staining was used to observe the morphology and number of neurons in the CA1 area of the rat hippocampus, Flow cytometry was used to detect the apoptosis of PC12 cells, PCR and Western blotting were used to detect the expression of Caspase3, miR-665 and GNB3/PI3K/AKT proteins. The target binding relationship between miR-665 and GNB3 was verified by double luciferase reporter gene experiment.</p></div><div><h3>Results</h3><p>In vivo experimental results showed that with the increase of Al(mal)<sub>3</sub> concentration, the escape latency of rats was prolonged, the target quadrant dwell time was shortened, and the number of crossing platform was reduced. Moreover, the arrangement of neurons was loose and the number decreased; the expression of Caspase3 and miR-665 increased, while the expression of GNB3/PI3K/AKT proteins decreased. In vitro experiments, with the increase of Al(mal)<sub>3</sub> concentration, apoptosis rate of PC12 cells increased, the expression of Caspase3, miR-665 and GNB3/PI3K/AKT proteins were consistent with rat results. After inhibiting miR-665 in the intervention group experiment, apoptosis rate of PC12 cells in the aluminum exposure group decreased, the expression of Caspase3 and miR-665 decreased, and the expression of GNB3/PI3K/AKT proteins increased.</p></div><div><h3>Conclusion</h3><p>MiR-665 plays an important role in aluminum induced neuronal apoptosis by targeting GNB3 and regulating the PI3K/AKT pathway.</p></div>\",\"PeriodicalId\":49970,\"journal\":{\"name\":\"Journal of Trace Elements in Medicine and Biology\",\"volume\":\"85 \",\"pages\":\"Article 127488\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-06-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Trace Elements in Medicine and Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0946672X24001081\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Trace Elements in Medicine and Biology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0946672X24001081","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
The mechanism of miR-665 targeting GNB3 in aluminum-induced neuronal apoptosis
Background
Aluminum exerts neurotoxic effects through various mechanisms, mainly manifested as impaired learning and memory function.
Methods
Forty SD rats were divided into 0, 10, 20, and 40 mM maltol aluminum [Al(mal)3] groups. Cell experiments are divided into 0, 100, 200, and 400 μM Al(mal)3 dose group and control, Al(mal)3, Al(mal)3+inhibitor NC, Al(mal)3+miR-665 inhibitor intervention group. Water maze was used to detect the learning and memory function of rats, HE staining was used to observe the morphology and number of neurons in the CA1 area of the rat hippocampus, Flow cytometry was used to detect the apoptosis of PC12 cells, PCR and Western blotting were used to detect the expression of Caspase3, miR-665 and GNB3/PI3K/AKT proteins. The target binding relationship between miR-665 and GNB3 was verified by double luciferase reporter gene experiment.
Results
In vivo experimental results showed that with the increase of Al(mal)3 concentration, the escape latency of rats was prolonged, the target quadrant dwell time was shortened, and the number of crossing platform was reduced. Moreover, the arrangement of neurons was loose and the number decreased; the expression of Caspase3 and miR-665 increased, while the expression of GNB3/PI3K/AKT proteins decreased. In vitro experiments, with the increase of Al(mal)3 concentration, apoptosis rate of PC12 cells increased, the expression of Caspase3, miR-665 and GNB3/PI3K/AKT proteins were consistent with rat results. After inhibiting miR-665 in the intervention group experiment, apoptosis rate of PC12 cells in the aluminum exposure group decreased, the expression of Caspase3 and miR-665 decreased, and the expression of GNB3/PI3K/AKT proteins increased.
Conclusion
MiR-665 plays an important role in aluminum induced neuronal apoptosis by targeting GNB3 and regulating the PI3K/AKT pathway.
期刊介绍：
The journal provides the reader with a thorough description of theoretical and applied aspects of trace elements in medicine and biology and is devoted to the advancement of scientific knowledge about trace elements and trace element species. Trace elements play essential roles in the maintenance of physiological processes. During the last decades there has been a great deal of scientific investigation about the function and binding of trace elements. The Journal of Trace Elements in Medicine and Biology focuses on the description and dissemination of scientific results concerning the role of trace elements with respect to their mode of action in health and disease and nutritional importance. Progress in the knowledge of the biological role of trace elements depends, however, on advances in trace elements chemistry. Thus the Journal of Trace Elements in Medicine and Biology will include only those papers that base their results on proven analytical methods.
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