Endocrine regulations最新文献

{"title":"The relationship between the tumor and its innervation: historical, methodical, morphological, and functional assessments - A minireview.","authors":"Filip Blasko, Lubica Horvathova","doi":"10.2478/enr-2024-0008","DOIUrl":"10.2478/enr-2024-0008","url":null,"abstract":"<p><p>The acceptance of the tumor as a non-isolated structure within the organism has opened a space for the study of a wide spectrum of potential direct and indirect interactions, not only between the tumor tissue and its vicinity, but also between the tumor and its macroenvironment, including the nervous system. Although several lines of evidence have implicated the nervous system in tumor growth and progression, for many years, researchers believed that tumors lacked innervation and the notion of indirect neuro-neoplastic interactions via other systems (e.g., immune, or endocrine) predominated. The original idea that tumors are supplied not only by blood and lymphatic vessels, but also autonomic and sensory nerves that may influence cancer progression, is not a recent phenomenon. Although in the past, mainly due to the insufficiently sensitive methodological approaches, opinions regarding the presence of nerves in tumors were inconsistent. However, data from the last decade have shown that tumors are able to stimulate the formation of their own innervation by processes called neo-neurogenesis and neo-axonogenesis. It has also been shown that tumor infiltrating nerves are not a passive, but active components of the tumor microenvironment and their presence in the tumor tissue is associated with an aggressive tumor phenotype and correlates with poor prognosis. The aim of the present review was to 1) summarize the available knowledge regarding the course of tumor innervation, 2) present the potential mechanisms and pathways for the possible induction of new nerve fibers into the tumor microenvironment, and 3) highlight the functional significance/consequences of the nerves infiltrating the tumors.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"58 1","pages":"68-82"},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of malignancy in Thy3 thyroid nodules.","authors":"Emad Mofid Nassif Rezkallah, Ragai Sobhi Hanna, Wael Magdy Elsaify","doi":"10.2478/enr-2024-0003","DOIUrl":"10.2478/enr-2024-0003","url":null,"abstract":"<p><p><b>Objective.</b> Thyroid cancer is the most common endocrine malignancy in humans. Ultrasound guided fine needle aspiration cytology (FNAC) is now considered the best diagnostic tool for the evaluation of any thyroid nodule. Thyroid cytology is graded from Thy1 to Thy5 with Thy3 being the most challenging in diagnosis. Our aim was to identify the risk of malignancy in Thy3 cytology in our centre. This risk should be explained to the patient before taking any decision. <b>Methods.</b> One hundred and one patients were included in our study. All patients had Thy3 cytology on preoperative ultrasound scan guided FNAC. All patients had diagnostic hemithyroidectomy. The results from the histology were compared with the cytology findings and the rates of malignancy were identified. <b>Results.</b> Of the 101 patients, 17 were males and 84 females. Average age for diagnosis was 52.4±15 years of age. Patients were classified into three groups; patient who had completely benign histology (n=70), patients who had incidental finding of micro-carcinoma after diagnostic hemithyroidectomy (n=10), and patients who had thyroid macro-carcinomas (n=21). Total rate of malignancy was 30.7% when combining both the malignant and the incidental groups and 20.8% when excluding the incidental group. <b>Conclusion.</b> Our rates of malignancy in Thy3 cytology are similar to the literature. These rates should be explained clearly to the patient during the preoperative counselling. Future advances in biomarkers technology may help to improve the preoperative diagnostic accuracy and reduce the rate of unnecessary thyroid surgery.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"58 1","pages":"19-25"},"PeriodicalIF":0.0,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cortisol controls endoplasmic reticulum stress and hypoxia dependent regulation of insulin receptor and related genes expression in HEK293 cells.","authors":"Dmytro O Minchenko, Olena O Khita, Yuliia M Viletska, Myroslava Y Sliusar, Olha V Rudnytska, Halyna E Kozynkevych, Borys H Bezrodnyi, Yevgen P Khikhlo, Oleksandr H Minchenko","doi":"10.2478/enr-2024-0001","DOIUrl":"10.2478/enr-2024-0001","url":null,"abstract":"<p><p><b>Objective.</b> Glucocorticoids are important stress-responsive regulators of insulin-dependent metabolic processes realized through specific changes in genome function. The aim of this study was to investigate the impact of cortisol on insulin receptor and related genes expression in HEK293 cells upon induction the endoplasmic reticulum (ER) stress by tunicamycin and hypoxia. <b>Methods.</b> The human embryonic kidney cell line HEK293 was used. Cells were exposed to cortisol (10 µM) as well as inducers of hypoxia (dimethyloxalylglycine, DMOG; 0.5 mM) and ER stress (tunicamycin; 0.2 µg/ml) for 4 h. The RNA from these cells was extracted and reverse transcribed. The expression level of <i>INSR</i>, <i>IRS2</i>, and <i>INSIG2</i> and some ER stress responsive genes encoding XBP1n, non-spliced variant, XBP1s, alternatively spliced variant of XBP1, and DNAJB9 proteins, was measured by quantitative polymerase chain reaction and normalized to ACTB. <b>Results.</b> We showed that exposure of HEK293 cells to cortisol elicited up-regulation in the expression of <i>INSR</i> and <i>DNAJB9</i> genes and down-regulation of XBP1s, XBP1n, IRS2, and INSIG2 mRNA levels. At the same time, induction of hypoxia by DMOG led to an up-regulation of the expression level of most studied mRNAs: XBP1s and XBP1n, IRS2 and INSIG2, but did not change significantly <i>INSR</i> and <i>DNAJB9</i> gene expression. We also showed that combined impact of cortisol and hypoxia introduced the up-regulation of INSR and suppressed XBP1n mRNA expression levels. Furthermore, the exposure of HEK293 cells to tunicamycin affected the expression of IRS2 gene and increased the level of XBP1n mRNA. At the same time, the combined treatment of these cells with cortisol and inductor of ER stress had much stronger impact on the expression of all the tested genes: strongly increased the mRNA level of ER stress dependent factors XBP1s and DNAJB9 as well as INSR and INSIG2, but down-regulated IRS2 and XBP1n. <b>Conclusion.</b> Taken together, the present study indicates that cortisol may interact with ER stress and hypoxia in the regulation of ER stress dependent <i>XBP1</i> and <i>DNAJB9</i> mRNA expression as well as INSR and its signaling and that this corticosteroid hormone modified the impact of hypoxia and especially tunicamycin on the expression of most studied genes in HEK293 cells. These data demonstrate molecular mechanisms of glucocorticoids interaction with ER stress and insulin signaling at the cellular level.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"58 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential of medicinal plants to ameliorate neovascularization activities in diabetes: A systematic review.","authors":"Phaik Har Yong, Shin Yee New, Meram Azzani, Yuan Seng Wu, Vi Vien Chia, Zhi Xiang Ng","doi":"10.2478/enr-2024-0004","DOIUrl":"10.2478/enr-2024-0004","url":null,"abstract":"<p><p>Hyperglycemia in diabetes mediates the release of angiogenic factors, oxidative stress, hypoxia, and inflammation, which in turn stimulate angiogenesis. Excessive angiogenesis can cause diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. All of these complications are debilitating, which may lead to an increased susceptibility to lower-limb amputations due to ulcerations and infections. In addition, microvascular alterations, segmental demyelination, and endoneurial microangiopathy may cause progressive deterioration ultimately leading to kidney failure and permanent blindness. Some medicinal plants have potent anti-angiogenic, antioxidant or anti-inflammatory properties that can ameliorate angiogenesis in diabetes. The purpose of this systematic review is to demonstrate the potential of medicinal plants in ameliorating the neovascularization activities in diabetes. Manuscripts were searched from PubMed, Science Direct, and Scopus databases, and Google Scholar was used for searching additional papers. From 1862 manuscripts searched, 1854 were excluded based on inclusion and exclusion criteria and 8 were included into this systematic review, whereas the required information was extracted and summarized. All identified medicinal plants decreased the high blood glucose levels in diabetes, except the aqueous extract of Lonicerae japonicae flos (FJL) and Vasant Kusumakar Ras. They also increased the reduced body weight in diabetes, except the aqueous extract of FL and total lignans from Fructus arctii. However, methanolic extract of Tinospora cordifolia and Vasant Kusumakar Ras were not tested for their ability to affect the body weight. Besides, all medicinal plants identified in this systematic review decreased the vascular endothelial growth factor (VEGF) protein expression and vasculature activity demonstrated by histopathological examination indicating promising anti-angiogenic properties. All medicinal plants identified in this systematic review have a potential to ameliorate neovascularization activities in diabetes by targeting the mechanistic pathways related to oxidative stress, inflammation, and angiogenesis.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"58 1","pages":"26-39"},"PeriodicalIF":0.0,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One-week sorghum (<i>Sorghum bicolor</i> L.) grain consumption is insufficient to increase adiponectin levels in prediabetic adults.","authors":"Sony Wibisono Mudjanarko, Teguh Rahardjo, Soebagijo Adi Soelistijo, Siti Rahmawati","doi":"10.2478/enr-2024-0002","DOIUrl":"10.2478/enr-2024-0002","url":null,"abstract":"<p><p><b>Objective.</b> Adiponectin is an internally produced bioactive compound with a protective role against the insulin resistance-related diseases. Finding an adiponectin modifier can play a beneficial role in preventing the progression of the diseases, particularly in the prediabetic patients, as a high-risk population. This study was undertaken to examine the effect of dietary sorghum grain for a week on the plasma adiponectin levels in prediabetic patients. <b>Methods.</b> The study involved 26 (13+13) participants in both control and intervention groups. The control group maintained their habitual diet of white rice, while the intervention group replaced their habitual diet of white rice with sorghum grain for seven consecutive days. In all participants, the adiponectin concentration was measured before and after the intervention period. <b>Results.</b> Most study subjects had central obesity and dyslipidemia. Adiponectin levels after the intervention period decreased from the baseline in the control and sorghum groups including in all BMI groups. The change of decreasing adiponectin level was greater in the control than the sorghum group and in line with greater BMI in the sorghum group, but statistically insignificant. No significant difference in adiponectin concentrations was found among BMI groups. <b>Conclusion.</b> Sorghum grain consumption for a week is insufficient to increase adiponectin levels in the prediabetic patients. Insulin resistance, central obesity, and dyslipidemia may be the confounding variables that alter the favorable effect of sorghum on adiponectin. Longer sorghum consumption or other interventions may be needed to increase the adiponectin levels in people under these conditions.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"58 1","pages":"11-18"},"PeriodicalIF":0.0,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of kisspeptin in the pathogenesis of a polycystic ovary syndrome.","authors":"Adiba Aasif, Roshan Alam, Haseeb Ahsan, Mohammad Mustufa Khan, Arshiya Khan, Saba Khan","doi":"10.2478/enr-2023-0032","DOIUrl":"10.2478/enr-2023-0032","url":null,"abstract":"<p><p>Hypothalamic-pituitary gonadal (HPG) axis is responsible for the development and regulation of the female reproductive system. In polycystic ovary syndrome (PCOS), there is a disturbance in the HPG axis. Kisspeptin, a neuropeptide produced by the KISS1 gene, plays a vital role in the regulation of HPG axis by binding with its receptors KISS1R/GPR54, and stimulates gonadotropin secretion from the hypothalamus into pituitary to release luteinizing hormone (LH) and follicle stimulating hormone (FSH). Polymorphisms or mutations in the KISS1 gene can cause disturbance in the kisspeptin signaling pathway and is thought to disrupt HPG axis. Altered signaling of kisspeptin can cause abnormal secretion of GnRH pulse, which leads to increased LH/FSH ratio, thereby affecting androgen levels and ovulation. The increased levels of androgen worsen the symptoms of PCOS. In the present article, we review the molecular physiology and pathology of kisspeptin and how it is responsible for the development of PCOS. The goal of this review article is to provide an overview and metabolic profile of kisspeptin in PCOS patients and the expression of kisspeptin in PCOS animal models. In the present article, we also review the molecular physiology and pathology of kisspeptin and how it is responsible for the development of PCOS.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"57 1","pages":"292-303"},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nicotinamide prevention in diabetes-induced alterations in the rat liver.","authors":"Tamara Kuchmerovska, Lesya Yanitska, Oksana Horkunenko, Mykhailo Guzyk, Tetiana Tykhonenko, Irina Pryvrotska","doi":"10.2478/enr-2023-0031","DOIUrl":"10.2478/enr-2023-0031","url":null,"abstract":"<p><p><b>Objective.</b> The study was performed to elucidate whether nicotinamide (NAm) can attenuate the diabetes-induced liver damage by correction of ammonia detoxifying function and disbalance of NAD-dependent processes in diabetic rats. <b>Methods.</b> After four weeks of streptozotocin-induced diabetes, Wistar male rats were treated for two weeks with or without NAm. Urea concentration, arginase, and glutamine synthetase activities, NAD+ levels, and NAD+/NADH ratio were measured in cytosolic liver extracts. Expression of <i>parp-1</i> gene in the liver was estimated by quantitative polymerase chain reaction and PARP-1 cleavage evaluated by Western blotting. <b>Results.</b> Despite the blood plasma lipid peroxidation products in diabetic rats were increased by 60%, the activity of superoxide dismutase (SOD) was reduced. NAm attenuated the oxidative stress, but did not affect the enzyme activity in diabetic rats. In liver of the diabetic rats, urea concentration and arginase activity were significantly higher than in the controls. The glutamine synthetase activity was decreased. Decline in NAD+ level and cytosolic NAD+/NADH ratio in the liver of diabetic rats was observed. Western blot analysis demonstrated a significant up-regulation of PARP-1 expression accompanied by the enzyme cleavage in the diabetic rat liver. However, no correlation was seen between mRNA expression of <i>parp-1</i> gene and PARP-1 protein in the liver of diabetic rats. NAm markedly attenuated PARP-1 cleavage induced by diabetes, but did not affect the <i>parp-1</i> gene expression. <b>Conclusions.</b> NAm counteracts diabetes-induced impairments in the rat liver through improvement of its detoxifying function, partial restoration of oxidative stress, NAD+ level, normalization of redox state of free cytosolic NAD+/NADH-couples, and prevention of PARP-1 cleavage.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"57 1","pages":"279-291"},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GHRL, LEP, LEPR genes polymorphism and their association with the metabolic syndrome in the Ukrainian population.","authors":"Andrii Prodan, Ihor Dzubanovsky, Oleksandr Kamyshnyi, Natalia Melnyk, Svitlana Pidruchna, Stanislava Voloshyn","doi":"10.2478/enr-2023-0030","DOIUrl":"10.2478/enr-2023-0030","url":null,"abstract":"<p><p><b>Objective.</b> Many conflicting results have been obtained in the study of leptin (LEP) and leptin receptor (LEPR) gene variants that are associated with the obesity and diabetes possibly due to differences in the study populations. The aim of this study was to evaluate changes in the metabolic hormones (leptin, ghrelin, adiponectin, resistin) levels in the blood of obese patients in relation to the GHRL (rs696217), LEP (rs7799039), LEPR (rs1137100, rs1137101, rs1805094) polymorphism in Ukrainian population. <b>Methods.</b> The study involved 53 obesity cases and 48 non-obesity subjects (controls). The GHRL, LEP, and LEPR genes polymorphism (rs696217, rs7799039, rs1137100, rs1137101, rs1805094) was genotyped using a TaqMan real-time polymerase chain reaction method. Blood hormones (leptin, ghrelin, adiponectin, resistin) were determined with commercially available kits using a Multiskan FC analyzer. <b>Results.</b> The study of the effect of genotypes of the GHRL (rs696217), LEP (rs7799039), and LEPR (rs1137100, rs1805094) polymorphisms on the level of metabolic hormones (leptin, ghrelin, adiponectin, resistin) in the blood of obese patients did not show reliably significant results. Thus, the presence of the LEPR genes (rs1137101) polymorphism in the Ukrainian population indicates an increased risk of the metabolic syndrome development regardless of the homozygous or heterozygous genotype (genotypes AA, AG, GG). <b>Conclusions.</b> We established a significant effect of the presence of the A allele and G allele of the LEPR gene polymorphism (rs1137101) on the level of leptin, ghrelin, adiponectin, and resistin in the serum of patients diagnosed with the metabolic syndrome in the Ukrainian population.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"57 1","pages":"269-278"},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of serum adipokines (omentin-1 and visfatin) in coronary artery disease at a North Indian hospital.","authors":"Saif Ali, Roshan Alam, Mohammad Kaleem Ahmad, Mukhtar Ahmad, Haseeb Ahsan, Mohammad Mustafa Khan, Saba Khan","doi":"10.2478/enr-2023-0029","DOIUrl":"10.2478/enr-2023-0029","url":null,"abstract":"<p><p><b>Objective.</b> Adipose tissue is considered to be an endocrine organ that secretes bioactive substances known as adipokines that contribute to the pathophysiology of metabolic and coronary diseases related to obesity. In this study, various novel biomarkers, such as inflammatory markers that are pro-inflammatory (visfatin) and anti-inflammatory (omentin-1), as prognostic indicators for people with coronary artery disease (CAD) were investigated. <b>Methods.</b> In this study, 30 diabetic patients with CAD, 30 diabetic patients without CAD, and 30 healthy control counterparts were included. Serum omentin and visfatin concentrations were evaluated by solid-phase enzyme linked immunosorbent assay (ELISA) kit. Patients with established diagnosis of CAD based on angiography, ECG, and elevated cardiac marker level were included into the study. Patients with cardioembolic stroke, cerebral venous sinus thrombosis, CNS vasculitis, and hemorrhage due to trauma, tumor, vascular malformation, and coagulopathy were excluded. <b>Results.</b> The serum omentin-1 levels were significantly higher in the healthy controls in comparison with the diabetic group (p<0.0001) and serum visfatin levels were significantly higher in the diabetic group in comparison with the healthy controls (p<0.0001). The serum omentin levels were significantly higher in the diabetic group in comparison with the cardio-diabetic group (p<0.0001) and serum visfatin levels were significantly higher in the cardio-diabetic group in comparison with the diabetic group (p<0.0001). The serum omentin-1 showed negative correlation with the serum visfatin in the cardio-diabetic group. <b>Conclusion.</b> The adipokines, such as omentin and visfatin, may be good therapeutic candidates in preventing or ameliorating CAD.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"57 1","pages":"262-268"},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia controls the expression of genes responsible for serine synthesis in U87MG cells on ERN1-dependent manner.","authors":"Myroslava Y Sliusar, Dmytro O Minchenko, Olena O Khita, Dariia O Tsymbal, Yuliia M Viletska, Olha Y Luzina, Serhij V Danilovskyi, Oksana O Ratushna, Oleksandr H Minchenko","doi":"10.2478/enr-2023-0028","DOIUrl":"10.2478/enr-2023-0028","url":null,"abstract":"<p><p><b>Objective.</b> Serine synthesis as well as endoplasmic reticulum stress and hypoxia are important factors of malignant tumor growth including glioblastoma. Previous studies have shown that the knockdown of ERN1 (endoplasmic reticulum to nucleus signaling) significantly suppressed the glioblastoma cell proliferation and modified the hypoxia regulation. The present study is aimed to investigate the impact of hypoxia on the expression of <i>PHGDH</i> (phosphoglycerate dehydrogenase), <i>PSAT1</i> (phosphoserine aminotransferase 1), <i>PSPH</i> (phosphoserine phosphatase), <i>ATF4</i> (activating transcription factor 4), and <i>SHMT1</i> (serine hydroxymethyltransferase 1) in U87MG glioblastoma cells in relation to knockdown of ERN1 with the intent to reveal the role of ERN1 signaling pathway on the endoplasmic reticulum stress-dependent regulation of expression of these genes. <b>Methods.</b> The control U87MG glioblastoma cells (transfected by empty vector) and ERN1 knockdown cells (transfected by dominant-negative ERN1) were exposed to hypoxia introduced by dimethyloxalylglycine for 4 h. RNA was extracted from cells and reverse transcribed. The expression level of <i>PHGDH</i>, <i>PSAT1</i>, <i>PDPH</i>, <i>SHMT1</i>, and <i>ATF4</i> genes was studied by real-time qPCR and normalized to ACTB. <b>Results.</b> It was found that hypoxia up-regulated the expression level of <i>PHGDH</i>, <i>PSAT1</i>, and <i>ATF4</i> genes in control U87MG cells, but <i>PSPH</i> and <i>SHMT1</i> genes expression was down-regulated. The expression of <i>PHGDH</i>, <i>PSAT1</i>, and <i>ATF4</i> genes in glioblastoma cells with knockdown of ERN1 signaling protein was more sensitive to hypoxia, especially <i>PSAT1</i> gene. At the same time, the expression of <i>PSPH</i> gene in ERN1 knockdown cells was resistant to hypoxia. The expression of <i>SHMT1</i> gene, encoding the enzyme responsible for conversion of serine to glycine, showed similar negative sensitivity to hypoxia in both control and ERN1 knockdown glioblastoma cells. <b>Conclusion.</b> The results of the present study demonstrate that the expression of genes responsible for serine synthesis is sensitive to hypoxia in gene-specific manner and that ERN1 knockdown significantly modifies the impact of hypoxia on the expression of <i>PHGDH</i>, <i>PSAT1</i>, <i>PSPH</i>, and <i>ATF4</i> genes in glioblastoma cells and reflects the ERN1-mediated reprograming of hypoxic regulation at gene expression level.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"57 1","pages":"252-261"},"PeriodicalIF":0.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41195395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}