scholarly journals Phosphorylation of Protein Kinase Akt by Mtorc2 in Peripheral Blood Mononuclear Cells of Patients with Cancer and Diabetes

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Tamara Sergeevnа Vatseba ◽  
Liubov Konstantinovna Sokolova ◽  
Victor Volodymyrovich Pushkarev ◽  
Olena Igorevna Kovzun ◽  
Vladimir Mikhailovich Pushkarev ◽  
...  

Akt/mTOR/p70S6K1 signaling pathway plays an important role in the pathogenesis of cancer and diabetes. Macrophages and lymphocytes are involved in the pathogenesis of diabetes, diabetic atherosclerosis, formation of insulin resistance as well as immune response to cancer and tumor maintenance. The aim of the study was to determine the Akt activation by mTORC2 in peripheral blood mononuclear cell (PBMC) of patients with type 2 diabetes and cancer.The following groups were studied: control group, patients with type 2 diabetes, cancer patients and patients with both cancer and diabetes. The amounts of phospho-Akt (р-S473) and phospho-p70S6K1 (p-T389) were determined using ELISA kits.The amount of phosphorylated Akt significantly increases in PBMC of patients with cancer. There was no effect in PBMC from patients with type 2 diabetes and significant decrease in the amount of phospho-Akt in PBMC of the patients group both with cancer and diabetes. p70S6K1 activation was observed in PBMC of the groups 2 and 3 patients.Thus, chronic diseases such as type 2 diabetes and cancer can affect the signaling mechanisms in blood cells. The state of Akt phosphorylation in leukocytes can indicate the activity of mTORC1 and its substrates, which may be important for the evaluation of the pathological process and the efficacy of the drugs. 

2013 ◽  
Vol 121 (06) ◽  
pp. 347-353 ◽  
Author(s):  
N. Corral-Fernández ◽  
M. Salgado-Bustamante ◽  
M. Martínez-Leija ◽  
N. Cortez-Espinosa ◽  
M. García-Hernández ◽  
...  

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1908
Author(s):  
Pradeep Bompada ◽  
Isabel Goncalves ◽  
Chuanyan Wu ◽  
Rui Gao ◽  
Jiangming Sun ◽  
...  

There is emerging evidence of an association between epigenetic modifications, glycemic control and atherosclerosis risk. In this study, we mapped genome-wide epigenetic changes in patients with type 2 diabetes (T2D) and advanced atherosclerotic disease. We performed chromatin immunoprecipitation sequencing (ChIP-seq) using a histone 3 lysine 9 acetylation (H3K9ac) mark in peripheral blood mononuclear cells from patients with atherosclerosis with T2D (n = 8) or without T2D (ND, n = 10). We mapped epigenome changes and identified 23,394 and 13,133 peaks in ND and T2D individuals, respectively. Out of all the peaks, 753 domains near the transcription start site (TSS) were unique to T2D. We found that T2D in atherosclerosis leads to an H3K9ac increase in 118, and loss in 63 genomic regions. Furthermore, we discovered an association between the genomic locations of significant H3K9ac changes with genetic variants identified in previous T2D GWAS. The transcription factor 7-like 2 (TCF7L2) rs7903146, together with several human leukocyte antigen (HLA) variants, were among the domains with the most dramatic changes of H3K9ac enrichments. Pathway analysis revealed multiple activated pathways involved in immunity, including type 1 diabetes. Our results present novel evidence on the interaction between genetics and epigenetics, as well as epigenetic changes related to immunity in patients with T2D and advanced atherosclerotic disease.


Author(s):  
О.В. Кочетова ◽  
Л.З. Ахмадишина ◽  
Д.Ш. Авзалетдинова ◽  
З.А. Шангареева ◽  
Г.Ф. Корытина

Сахарный диабет 2 типа (СД2) - метаболическое многофакторное, генетически обусловленное, опасное для жизни заболевание. Развитие осложнений связано с хроническим иммуновоспалительным процессом и с образованием иммунных комплексов. Целью исследования явился анализ профиля экспрессии комплекса функционально взаимосвязанных генов (цитокинов, хемокинов и другие ключевые молекулы воспалительного ответа) в мононуклеарах периферической крови у пациентов с СД2 (N=10) и в контрольной группе (N=10). Пациенты и контроль были подобраны по полу, возрасту, принадлежали к этнической группе татар. Профиль экспрессии 84 генов иммунного ответа исследовали методом OT-ПЦР на приборе BioRad CFX96TM набором RT2 Profiler PCR Arrays «Human Cytokines & Chemokines PCR Array» (Qiagen). Значимые изменения экспрессии (p<0,05) в общей группе больных СД2 по сравнению с контролем были установлены для генов FASLG, IL16, OSM, CSF1, CXCL16, BMP6. При этом профиль экспрессии этих генов у больных СД2 характеризуется повышением уровня от 2,1 до 6,7 раз по сравнению со здоровыми индивидами. Профиль экспрессии генов CXCL8, CXCL1, CXCL2, CXCL10, CCL2, IL1RN характеризуется снижением уровня от 2,1 до 8,78 раз по сравнению со здоровыми индивидами. Значимые статистические различия при снижении экспрессии были получены для генов IL1RN (fold-change (FCh)=-3,31, p=0,013), CXCL1 (FCh=-2,74, p=0,027), CXCL2 (FCh=-2,66, p=0,038). Наиболее значимое повышение транскрипционной активности было показано для генов IL16 (FCh=6,72, p=0,037) и FASLG (FCh=2,83 p=0,034) среди больных СД2 по сравнению с контрольной группой. Type 2 diabetes mellitus (T2DM) is a metabolic multifactorial, genetically determined, life-threatening disease. The development of complications is associated with a chronic immuno-inflammatory process and with the formation of immune complexes. The aim of the study was to analyze the expression profile of a complex of functionally interconnected genes (cytokines, chemokines, and other key molecules of the inflammatory response) in peripheral blood mononuclear cells in patients with T2DM (N = 10) and in the control group (N = 10). Patients and controls were matched by gender, age, and belonged to the Tatars ethnic group. The expression profile of 84 immune response genes was studied by OT-PCR on a BioRad CFX96TM instrument using the Human Cytokines & Chemokines PCR Array RT2 Profiler PCR Arrays kit (Qiagen). Significant changes in expression (p <0.05) in the general group of patients with T2DM compared with the control were found for the FASLG, IL16, OSM, CSF1, CXCL16, BMP6 genes. Moreover, the expression profile of these genes in patients with type 2 diabetes is characterized by an increase in the level from 2.1 to 6.7 times in comparison with healthy individuals. The gene expression profile of CXCL8, CXCL1, CXCL2, CXCL10, CCL2, IL1RN is characterized by a decrease in the level from 2.1 to 8.78 times in comparison with healthy individuals. Significant statistical differences with a decrease in expression were obtained for the genes IL1RN (fold-change (FCh) = - 3.31, p = 0.013), CXCL1 (FCh = -2.74, p = 0.027), CXCL2 (FCh = -2.66, p = 0.038) . The most significant increase in transcriptional activity was shown for the genes IL16 (FCh = 6.72, p = 0.037) and FASLG (FCh = 2.83 p = 0.034) among patients with type 2 diabetes compared with the control group.


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