Graded Differentiation of Glioma in GSK-3 β: The Study and Analysis of the Expression Difference and Its Significance in the Endoplasmic Reticulum Stress Apoptosis Pathway
Hong Song, Guoliang Mao, Nanlin Jiao, Wanwan Gao, Rui Pang
{"title":"Graded Differentiation of Glioma in GSK-3 β: The Study and Analysis of the Expression Difference and Its Significance in the Endoplasmic Reticulum Stress Apoptosis Pathway","authors":"Hong Song, Guoliang Mao, Nanlin Jiao, Wanwan Gao, Rui Pang","doi":"10.1134/s1819712424020156","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Glioma accounts for 80% of malignant central nervous system, with high incidence and extremely difficult to cure. However, for the role of ER stress apoptosis in tumor has caused great attention, the neuronal polarity molecule glycogen synthase kinase-3 β(GSK-3 β) endoplasmic network stress apoptosis pathway in tumor mechanism is a hot research in recent years, but for GSK-3 β ER stress apoptosis pathway in different levels of glioma research is extremely rare. In this experiment, we jointly explored the significance of GSK-3 β ER apoptosis pathway in different grades of glioma, which provided a strong basis for the precise treatment of glioma. 35 inpatients from December 2021 to December 2022 were enrolled into the different grades of glioma group and the normal control group. Tumor tissue was classified according to medical pathology. The other five normal brain tissues were obtained from the normal brain tissue of the fistula created in non-functional areas. One of the brain samples was stored for the apoptosis index (AI) of TUNEL (chromogenic method), and another part was stored in liquid nitrogen for the expression of GRP78, IRE 1, ATF 6, PERK, p-Tyr216-GSK-3 β, p-Ser 9-GSK-3 β, and Caspase-3. The AI values of different grades of glioma and normal control groups showed that the normal control, low-grade glioma and high-grade glioma groups were 8. 131 ± 0.234, 68.523 ± 1.392 and 22. 421 ± 0.236, respectively. The AI value was higher in the glioma group than in the normal controls (<i>P</i> < 0.05), while the AI value in the glioma group was negatively correlated with its malignancy (<i>r</i> = –0.725, <i>P</i> = 0.000). Western blot showed: compared with the normal control group, apoptosis initiation protein GRP78 expression, IRE 1, ATF 6, PERK decreased (<i>P</i> < 0.05); pathway key protein p-Ser 9-GSK-3 β increased, and p-Tyr216-GSK-3 β decreased (<i>P</i> < 0.05); pathway executive protein Caspase-3 increased (<i>P</i> < 0.05). However, the apoptosis initiation protein GRP78, IRE 1, ATF 6, PERK increased (<i>P</i> < 0.05); pathway key protein p-Ser 9-GSK-3 β decreased and p-Tyr216-GSK-3 β was increased (<i>P</i> < 0.05); pathway execution protein Caspase-3 expression decreased (<i>P</i> < 0.05). Conclusion: the AI value of low-grade glioma is higher than that of high-grade glioma, indicating that the progression of brain glioma may inhibit cell apoptosis. The increased apoptosis index and the expression changes of GSK-3 β ER stress cell apoptosis pathway in the glioma group indicate that the apoptosis pathway in GSK-3 β ER stress cells was initiated and executed in glioma. In low-grade glioma cells, there may be a mechanism to inhibit IRE 1, ATF 6, PERK, and p-Tyr216-GSK-3 β expression, which further promotes cell apoptosis and inhibited tumor progression. And with the progression of glioma, The expression of IRE 1, ATF 6, PERK, GRP78, and p-Tyr216-GSK-3 β was gradually increased, The expression of P-Ser 9-GSK-3 β, Caspase-3 was gradually decreased, It indicates that GRP78, IRE 1, ATF 6, PERK and p-Tyr216-GSK-3 β may be involved in the progression of glioma; Meanwhile, brain glioma cells may, by inhibiting the expression of P-Ser 9-GSK-3 β and the apoptosis executive protein Caspase-3, Further inhibited the apoptosis of brain glioma cells, promoted the progression of brain glioma. Inhibiting the expression of IRE 1, ATF 6, PERK, GRP78 and p‑Tyr216-GSK-3 β may be of great significance to inhibiting the progression of glioma, which provides a strong basis for guiding the precision treatment of clinical glioma.</p>","PeriodicalId":19119,"journal":{"name":"Neurochemical Journal","volume":null,"pages":null},"PeriodicalIF":0.5000,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurochemical Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1134/s1819712424020156","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Glioma accounts for 80% of malignant central nervous system, with high incidence and extremely difficult to cure. However, for the role of ER stress apoptosis in tumor has caused great attention, the neuronal polarity molecule glycogen synthase kinase-3 β(GSK-3 β) endoplasmic network stress apoptosis pathway in tumor mechanism is a hot research in recent years, but for GSK-3 β ER stress apoptosis pathway in different levels of glioma research is extremely rare. In this experiment, we jointly explored the significance of GSK-3 β ER apoptosis pathway in different grades of glioma, which provided a strong basis for the precise treatment of glioma. 35 inpatients from December 2021 to December 2022 were enrolled into the different grades of glioma group and the normal control group. Tumor tissue was classified according to medical pathology. The other five normal brain tissues were obtained from the normal brain tissue of the fistula created in non-functional areas. One of the brain samples was stored for the apoptosis index (AI) of TUNEL (chromogenic method), and another part was stored in liquid nitrogen for the expression of GRP78, IRE 1, ATF 6, PERK, p-Tyr216-GSK-3 β, p-Ser 9-GSK-3 β, and Caspase-3. The AI values of different grades of glioma and normal control groups showed that the normal control, low-grade glioma and high-grade glioma groups were 8. 131 ± 0.234, 68.523 ± 1.392 and 22. 421 ± 0.236, respectively. The AI value was higher in the glioma group than in the normal controls (P < 0.05), while the AI value in the glioma group was negatively correlated with its malignancy (r = –0.725, P = 0.000). Western blot showed: compared with the normal control group, apoptosis initiation protein GRP78 expression, IRE 1, ATF 6, PERK decreased (P < 0.05); pathway key protein p-Ser 9-GSK-3 β increased, and p-Tyr216-GSK-3 β decreased (P < 0.05); pathway executive protein Caspase-3 increased (P < 0.05). However, the apoptosis initiation protein GRP78, IRE 1, ATF 6, PERK increased (P < 0.05); pathway key protein p-Ser 9-GSK-3 β decreased and p-Tyr216-GSK-3 β was increased (P < 0.05); pathway execution protein Caspase-3 expression decreased (P < 0.05). Conclusion: the AI value of low-grade glioma is higher than that of high-grade glioma, indicating that the progression of brain glioma may inhibit cell apoptosis. The increased apoptosis index and the expression changes of GSK-3 β ER stress cell apoptosis pathway in the glioma group indicate that the apoptosis pathway in GSK-3 β ER stress cells was initiated and executed in glioma. In low-grade glioma cells, there may be a mechanism to inhibit IRE 1, ATF 6, PERK, and p-Tyr216-GSK-3 β expression, which further promotes cell apoptosis and inhibited tumor progression. And with the progression of glioma, The expression of IRE 1, ATF 6, PERK, GRP78, and p-Tyr216-GSK-3 β was gradually increased, The expression of P-Ser 9-GSK-3 β, Caspase-3 was gradually decreased, It indicates that GRP78, IRE 1, ATF 6, PERK and p-Tyr216-GSK-3 β may be involved in the progression of glioma; Meanwhile, brain glioma cells may, by inhibiting the expression of P-Ser 9-GSK-3 β and the apoptosis executive protein Caspase-3, Further inhibited the apoptosis of brain glioma cells, promoted the progression of brain glioma. Inhibiting the expression of IRE 1, ATF 6, PERK, GRP78 and p‑Tyr216-GSK-3 β may be of great significance to inhibiting the progression of glioma, which provides a strong basis for guiding the precision treatment of clinical glioma.
期刊介绍：
Neurochemical Journal (Neirokhimiya) provides a source for the communication of the latest findings in all areas of contemporary neurochemistry and other fields of relevance (including molecular biology, biochemistry, physiology, neuroimmunology, pharmacology) in an afford to expand our understanding of the functions of the nervous system. The journal presents papers on functional neurochemistry, nervous system receptors, neurotransmitters, myelin, chromaffin granules and other components of the nervous system, as well as neurophysiological and clinical aspects, behavioral reactions, etc. Relevant topics include structure and function of the nervous system proteins, neuropeptides, nucleic acids, nucleotides, lipids, and other biologically active components.
The journal is devoted to the rapid publication of regular papers containing the results of original research, reviews highlighting major developments in neurochemistry, short communications, new experimental studies that use neurochemical methodology, descriptions of new methods of value for neurochemistry, theoretical material suggesting novel principles and approaches to neurochemical problems, presentations of new hypotheses and significant findings, discussions, chronicles of congresses, meetings, and conferences with short presentations of the most sensational and timely reports, information on the activity of the Russian and International Neurochemical Societies, as well as advertisements of reagents and equipment.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
