scholarly journals TNF-αand IFN-s-Dependent Muscle Decay Is Linked to NF-κB- and STAT-1α-StimulatedAtrogin1andMuRF1Genes in C2C12 Myotubes

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Barbara Pijet ◽  
Maja Pijet ◽  
Anna Litwiniuk ◽  
Małgorzata Gajewska ◽  
Beata Pająk ◽  
...  
Keyword(s):  
Protein Expression ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
C2c12 Cells ◽  
Metabolic Inhibitors ◽  
C2c12 Myotubes ◽  
Protein Expression Level ◽  
C2c12 Myoblasts ◽  
Stat Signaling ◽  
Increased Activity

TNF-αwas shown to stimulate mitogenicity in C2C12 myoblasts. Selected cytokines TNF-α, IFNα, or IFNγreduced the expression of myosin heavy chain (MyHC IIa) when given together. Molecular mechanisms of cytokine activities were controlled by NF-κB and JAK/STAT signaling pathways, as metabolic inhibitors, curcumin and AG490, inhibited some of TNF-αand IFNα/IFNγeffects. Insulin was hardly antagonistic to TNF-α- and IFNα/IFNγ-dependent decrease in MyHC IIa protein expression. Cytokines used individually or together also repressed myogenesis of C2C12 cells. Moreover, TNF-α- and IFNα/IFNγ-dependent effects on C2C12 myotubes were associated with increased activity ofAtrogin1andMuRF1genes, which code ubiquitin ligases.MyHC IIagene activity was unaltered by cytokines. Inhibition of NF-κB or JAK/STAT with specific metabolic inhibitors decreased activity ofAtrogin1andMuRF1but notMyHC IIagene. Overall, these results suggest cooperation between cytokines in the reduction of MyHC IIa protein expression level via NF-κB/JAK/STAT signaling pathways and activation ofAtrogin1andMuRF1genes as their molecular targets. Insulin cotreatment or pretreatment does not protect against muscle decay induced by examined proinflammatory cytokines.

Interleukin-6 stimulates α-MG uptake in renal proximal tubule cells: involvement of STAT3, PI3K/Akt, MAPKs, and NF-κB

2007 ◽  
Vol 293 (4) ◽  
pp. F1036-F1046 ◽  
Author(s):  
Yu Jin Lee ◽  
Jung Sun Heo ◽  
Han Na Suh ◽  
Min Young Lee ◽  
Ho Jae Han
Keyword(s):  
Protein Expression ◽  
Proximal Tubule ◽  
Signaling Pathways ◽  
Interleukin 6 ◽  
Renal Proximal Tubule ◽  
Expression Level ◽  
Protein Expression Level ◽  
Proximal Tubule Cells ◽  
Tubule Cells ◽  
Renal Proximal Tubule Cells

Recent studies have shown that interleukin 6 (IL-6) acts on the cellular proliferation-activating transduction signals during cellular regeneration. Therefore, this study examined the effect of IL-6 on the activation of Na+/glucose cotransporters (SGLTs) and its related signaling pathways in primary cultured renal proximal tubule cells (PTCs). IL-6 increased the level of α-methyl-d-[14C]glucopyranoside (α-MG) uptake in time- and dose-dependent manners. IL-6 also increased SGLT1 plus SGLT2 mRNA and protein expression level. The IL-6 receptors (IL-6Rα and gp130) were expressed in PTCs. In addition, genistein and herbimycin A completely blocked the IL-6-induced increases in α-MG uptake and the protein expression level of SGLTs. On the other hand, IL-6 increased the level of 5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate-sensitive cellular reactive oxygen species (ROS), and IL-6-induced increases in α-MG uptake and the protein expression level of SGLTs were blocked by ascorbic acid or taurine (antioxidants). IL-6 also increased the phosphorylation of signal transducer and activator of transcription-3 (STAT3), phosphoinositide-3 kinase (PI3K)/Akt, and mitogen-activated protein kinases (MAPKs) in a time-dependent manner. A pretreatment with STAT3 inhibitor LY 294002, an Akt inhibitor, or MAPK inhibitors significantly blocked the IL-6-induced increase in α-MG uptake. In addition, IL-6 increased the level of nuclear factor-κB (NF-κB) phosphorylation. A pretreatment with SN50 or BAY 11-7082 also blocked the IL-6-induced increase in α-MG uptake. In conclusion, IL-6 increases the SGLT activity through ROS, and its action in renal PTCs is associated with the STAT3, PI3K/Akt, MAPKs, and NF-κB signaling pathways.

scholarly journals Diverse Action of Selected Statins on Skeletal Muscle Cells—An Attempt to Explain the Protective Effect of Geranylgeraniol (GGOH) in Statin-Associated Myopathy (SAM)

2019 ◽  
Vol 8 (5) ◽  
pp. 694 ◽  
Author(s):  
Anna Jaśkiewicz ◽  
Beata Pająk ◽  
Magdalena Łabieniec-Watała ◽  
Clara De Palma ◽  
Arkadiusz Orzechowski
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Cell Viability ◽  
Mitochondrial Respiration ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
C2c12 Cell ◽  
Muscle Cells ◽  
C2c12 Cells ◽  
Calpain Inhibitor

The present study is centered on molecular mechanisms of the cytoprotective effect of geranylgeraniol (GGOH) in skeletal muscle harmed by statin-associated myopathy (SAM). GGOH via autophagy induction was purportedly assumed to prevent skeletal muscle viability impaired by statins, atorvastatin (ATR) or simvastatin (SIM). The C2C12 cell line was used as the ‘in vitro’ model of muscle cells at different stages of muscle formation, and the effect of ATR or SIM on the cell viability, protein expression and mitochondrial respiration were tested. Autophagy seems to be important for the differentiation of muscle cells; however, it did not participate in the observed GGOH cytoprotective effects. We showed that ATR- and SIM-dependent loss in cell viability was reversed by GGOH co-treatment, although GGOH did not reverse the ATR-induced drop in the cytochrome c oxidase protein expression level. It has been unambiguously revealed that the mitochondria of C2C12 cells are not sensitive to SIM, although ATR effectively inhibits mitochondrial respiration. GGOH restored proper mitochondria functioning. Apoptosis might, to some extent, explain the lower viability of statin-treated myotubes as the pan-caspase inhibitor, N-Benzyloxycarbonyl-Val-Ala-Asp(O-Me) fluoromethyl ketone (Z-VAD-FMK), partly reversed ATR- or SIM-induced cytotoxic effects; however, it does not do so in conjunction with caspase-3. It appears that the calpain inhibitor, N-Acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLM), restored the viability that was reduced by ATR and SIM (p < 0.001). GGOH prevents SAM, in part, as a consequence of a caspase-3 independent pathway, probably by calpain system inactivation.

scholarly journals Characterization of the ATP-hydrolysing activity of α-sarcoglycan

2004 ◽  
Vol 381 (1) ◽  
pp. 105-112 ◽  
Author(s):  
Dorianna SANDONÀ ◽  
Stefano GASTALDELLO ◽  
Tiziana MARTINELLO ◽  
Romeo BETTO
Keyword(s):  
Muscular Dystrophy ◽  
Molecular Mechanisms ◽  
C2c12 Cells ◽  
C2c12 Myotubes ◽  
Atp Binding ◽  
Binding Motif ◽  
Nucleotidase Activity ◽  
Reactive Blue 2 ◽  
Definitive Evidence ◽  
Dystrophin Complex

α-Sarcoglycan is a glycoprotein associated with the dystrophin complex at sarcolemma of skeletal and cardiac muscles. Gene defects in α-sarcoglycan lead to a severe muscular dystrophy whose molecular mechanisms are not yet clear. A first insight into the function of α-sarcoglycan was obtained by finding that it is an ATP-binding protein and that it probably confers ability to hydrolyse ATP to the purified dystrophin complex [Betto, Senter, Ceoldo, Tarricone, Biral and Salviati (1999) J. Biol. Chem. 274, 7907–7912]. In the present study, we present definitive evidence showing that α-sarcoglycan is an ATP-hydrolysing enzyme. The appearance of α-sarcoglycan protein expression was correlated with the increase in ecto-nucleotidase activity during differentiation of C2C12 cells. Approx. 25% of ecto-nucleotidase activity displayed by the C2C12 myotubes was inhibited by preincubating cells with an antibody specific for the ATP-binding motif of α-sarcoglycan. This demonstrates that α-sarcoglycan substantially contributes to total ecto-nucleotidase activity of C2C12 myotubes. To characterize further this activity, human embryonic kidney 293 cells were transfected with expression plasmids containing α-sarcoglycan cDNA. Transfected cells exhibited a significant increase in the ATP-hydrolysing activity that was abolished by the anti-α-sarcoglycan antibody. The enzyme had a substrate specificity for ATP and ADP, did not hydrolyse other triphosphonucleosides, and the affinity for ATP was in the low mM range. The ATPase activity strictly required the presence of both Mg2+ and Ca2+ and was completely inhibited by suramin and reactive blue-2. These results show that α-sarcoglycan is a Ca2+, Mg2+-ecto-ATPDase. The possible consequences of the absence of α-sarcoglycan activity in the pathogenesis of muscular dystrophy are discussed.

scholarly journals Regulation of the Intracellular Localization of Foxo3a by Stress-Activated Protein Kinase Signaling Pathways in Skeletal Muscle Cells

2009 ◽  
Vol 30 (2) ◽  
pp. 470-480 ◽  
Author(s):  
Stephan Clavel ◽  
Sandrine Siffroi-Fernandez ◽  
Anne Sophie Coldefy ◽  
Kim Boulukos ◽  
Didier F. Pisani ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Muscle Atrophy ◽  
Nuclear Import ◽  
Nuclear Export ◽  
Nuclear Translocation ◽  
Muscle Cells ◽  
C2c12 Cells ◽  
C2c12 Myotubes

ABSTRACT Muscle atrophy is a debilitating process associated with many chronic wasting diseases, like cancer, diabetes, sepsis, and renal failure. Rapid loss of muscle mass occurs mainly through the activation of protein breakdown by the ubiquitin proteasome pathway. Foxo3a transcription factor is critical for muscle atrophy, since it activates the expression of ubiquitin ligase Atrogin-1. In several models of atrophy, inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway induces nuclear import of Foxo3a through an Akt-dependent process. This study aimed to identify signaling pathways involved in the control of Foxo3a nuclear translocation in muscle cells. We observed that after nuclear import of Foxo3a by PI3K/Akt pathway inhibition, activation of stress-activated protein kinase (SAPK) pathways induced nuclear export of Foxo3a through CRM1. This mechanism involved the c-Jun NH2-terminal kinase (JNK) signaling pathway and was independent of Akt. Likewise, we showed that inhibition of p38 induced a massive nuclear relocalization of Foxo3a. Our results thus suggest that SAPKs are involved in the control of Foxo3a nucleocytoplasmic translocation in C2C12 cells. Moreover, activation of SAPKs decreases the expression of Atrogin-1, and stable C2C12 myotubes, in which the p38 pathway is constitutively activated, present partial protection against atrophy.

scholarly journals Morin Induces Melanogenesis via Activation of MAPK Signaling Pathways in B16F10 Mouse Melanoma Cells

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2150
Author(s):  
SeoYeon Shin ◽  
JaeYeon Ko ◽  
MinJeong Kim ◽  
Nuri Song ◽  
KyungMok Park
Keyword(s):  
Protein Expression ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Melanoma Cells ◽  
Mapk Signaling ◽  
Tyrosinase Activity ◽  
Melanin Biosynthesis ◽  
Mouse Melanoma ◽  
Melanin Contents ◽  
Mapk Signaling Pathways

Morin is a well-known flavonoid, and has been reported to have various properties, such as anti-cell death, antioxidant, and anti-inflammatory properties. Although studies on the biochemical and biological actions of morin have been reported, the melanin biosynthesis effects and molecular mechanisms are unknown. In this study, we first found that morin has the effect of enhancing melanin biosynthesis in B16F10 mouse melanoma cells, and analyzed the molecular mechanism. In this study, we examined the effects of morin on the melanin contents and tyrosinase activity, as well as the protein expression levels of the melanogenic enzymes TRP-1, TRP-2, and microphtalmia-associated transcription factor (MITF) in B16F10 mouse melanoma cells. Morin showed no cytotoxicity in the concentration range of 5–100 μM, and significantly increased the intracellular tyrosinase activity and melanin contents. In mechanism analysis, morin increased the protein expression of TRP-1, TRP-2, and MITF associated with melanogenesis. Furthermore, morin increased phosphorylated ERK and p38 at the early time, and decreased phosphorylated ERK after 12 h. The results suggest that morin enhances melanin synthesis through the MAPK signaling pathways in B16F10 mouse melanoma cells.

scholarly journals Robust intrinsic differences in mitochondrial respiration and H2O2 emission between L6 and C2C12 cells

2019 ◽  
Vol 317 (2) ◽  
pp. C339-C347 ◽  
Author(s):  
Matthew M. Robinson ◽  
Bergen K. Sather ◽  
Emily R. Burney ◽  
Sarah E. Ehrlicher ◽  
Harrison D. Stierwalt ◽  
...  
Keyword(s):  
Electron Transfer ◽  
Oxygen Consumption ◽  
Oxidative Phosphorylation ◽  
Cell Lines ◽  
C2c12 Cell ◽  
Mitochondrial Metabolism ◽  
C2c12 Cells ◽  
C2c12 Myotubes ◽  
Acid Oxidation ◽  
C2c12 Myoblasts

Rat L6 and mouse C2C12 cell lines are commonly used to investigate myocellular metabolism. Mitochondrial characteristics of these cell lines remain poorly understood despite mitochondria being implicated in the development of various metabolic diseases. To address this need, we performed high-resolution respirometry to determine rates of oxygen consumption and H2O2 emission in suspended myoblasts during multiple substrate-uncoupler-inhibitor titration protocols. The capacity for oxidative phosphorylation supported by glutamate and malate, with and without succinate, or supported by palmitoyl-l-carnitine was lower in L6 compared with C2C12 myoblasts (all P < 0.01 for L6 vs. C2C12). Conversely, H2O2 emission during oxidative phosphorylation was greater in L6 than C2C12 myoblasts ( P < 0.01 for L6 vs. C2C12). Induction of noncoupled respiration revealed a significantly greater electron transfer capacity in C2C12 compared with L6 myoblasts, regardless of the substrate(s) provided. Mitochondrial metabolism was also investigated in differentiated L6 and C2C12 myotubes. Basal rates of oxygen consumption were not different between intact, adherent L6, and C2C12 myotubes; however, noncoupled respiration was significantly lower in L6 compared with C2C12 myotubes ( P = 0.01). In summary, L6 myoblasts had lower respiration rates than C2C12 myoblasts, including lesser capacity for fatty acid oxidation and greater electron leak toward H2O2. L6 cells also retain a lower capacity for electron transfer compared with C2C12 following differentiation to form fused myotubes. Intrinsic differences in mitochondrial metabolism between these cell lines should be considered when modeling and investigating myocellular metabolism.

scholarly journals The Roles of Immune Cells in the Pathogenesis of Fibrosis

2020 ◽  
Vol 21 (15) ◽  
pp. 5203 ◽  
Author(s):  
Enyu Huang ◽  
Na Peng ◽  
Fan Xiao ◽  
Dajun Hu ◽  
Xiaohui Wang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathways ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Adaptive Immune ◽  
Recent Advances ◽  
Adaptive Immune Cells ◽  
Stat Signaling ◽  
Fibrotic Diseases

Tissue injury and inflammatory response trigger the development of fibrosis in various diseases. It has been recognized that both innate and adaptive immune cells are important players with multifaceted functions in fibrogenesis. The activated immune cells produce various cytokines, modulate the differentiation and functions of myofibroblasts via diverse molecular mechanisms, and regulate fibrotic development. The immune cells exhibit differential functions during different stages of fibrotic diseases. In this review, we summarized recent advances in understanding the roles of immune cells in regulating fibrotic development and immune-based therapies in different disorders and discuss the underlying molecular mechanisms with a focus on mTOR and JAK-STAT signaling pathways.

scholarly journals Ang-(1–7) protects skeletal muscle function in aged mice

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ying Li ◽  
Jiao Song ◽  
Yangyang Jiang ◽  
Xue Yang ◽  
Li Cao ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Muscle Function ◽  
Molecular Mechanisms ◽  
C2c12 Cells ◽  
Skeletal Muscle Function ◽  
Protective Function ◽  
Aged Mice ◽  
Age Related ◽  
The Impact

Abstract Background The angiotensin-converting enzyme 2 (ACE2)/angiotensin 1–7 (Ang-(1–7)) axis has been shown to protect against the age-associated decline in skeletal muscle function. Here, we investigated the protective effects of ACE2 in mitigating the age-associated decline of skeletal muscle function and to identify the potential underlying molecular mechanisms. Methods We measured the expression levels of Ang-(1–7) in C57BL/6J mice of different ages and correlated these levels with measures of skeletal muscle function. We also investigated the expression of myocyte enhancer factor 2 A (MEF2A) in ACE2 knockout (ACE2KO) mice and its relationship with muscle function. We then treated aged ACE2KO mice for four weeks with Ang-(1–7) and characterized the levels of MEF2A and skeletal muscle function before and after treatment. We assessed the impact of Ang-(1–7) on the growth and differentiation of C2C12 cells in vitro and assessed changes in expression of the glucose transporter type 4 (Glut4). Results Aged mice showed reduced skeletal muscle function and levels of Ang-(1–7) expression in comparison to young and middle-aged mice. In ACE2KO mice, skeletal muscle function and MEF2A protein expression were significantly lower than in age-matched wild-type (WT) mice. After one month of Ang-(1–7) treatment, skeletal muscle function in the aged ACE2KO mice improved, while MEF2A protein expression was similar to that in the untreated group. In C2C12 cells, Ang-(1–7) was shown to promote along with the upregulated expression of Glut4. Conclusions The ACE2/ Ang-(1–7) axis has a protective function in skeletal muscle and administration of exogenous Ang-(1–7) can delay the age-related decline in the function of skeletal muscle.

scholarly journals Prion Infection of Muscle Cells In Vitro

2007 ◽  
Vol 81 (9) ◽  
pp. 4615-4624 ◽  
Author(s):  
Wendy M. Dlakic ◽  
Eric Grigg ◽  
Richard A. Bessen
Keyword(s):  
Skeletal Muscle ◽  
Cell Line ◽  
Muscle Cells ◽  
C2c12 Cells ◽  
C2c12 Myotubes ◽  
C2c12 Myoblasts ◽  
Peripheral Cell ◽  
Prion Infection

ABSTRACT The prion agent has been detected in skeletal muscle of humans and animals with prion diseases. Here we report scrapie infection of murine C2C12 myoblasts and myotubes in vitro following coculture with a scrapie-infected murine neuroblastoma (N2A) cell line but not following incubation with a scrapie-infected nonneuronal cell line or a scrapie brain homogenate. Terminal differentiation of scrapie-infected C2C12 myoblasts into myotubes resulted in an increase in the expression of the disease-specific prion protein, PrPSc. The amount of scrapie infectivity or PrPSc in C2C12 myotubes was comparable to the levels found in scrapie-infected N2A cells, indicating that a high level of infection was established in muscle cells. Subclones of scrapie-infected C2C12 cells produced high levels of PrPSc in myotubes, and the C-terminal C2 polypeptide fragment of PrPSc was found based on deglycosylation and PrPSc-specific immunoprecipitation of cell lysates. This is the first report of a stable prion infection in muscle cells in vitro and of a long-term prion infection in a nondividing, differentiated peripheral cell type in culture. These in vitro studies also suggest that in vivo prion infection of skeletal muscle requires contact with prion-infected neurons or, possibly, nerve terminals.

scholarly journals Взаимосвязи между продукцией тимозина 1α и состоянием внутриклеточных сигнальных механизмов в мононуклеарных лейкоцитах периферической крови при артериальной гипертензии

2020 ◽  
Author(s):  
A.V. Logatkina ◽  
I.V. Terekhov ◽  
V.S. Nikiforov ◽  
S.S. Bondar
Keyword(s):  
Transcription Factor ◽  
Signaling Pathways ◽  
Protein Kinases ◽  
Intracellular Signaling ◽  
Linear Regression Analysis ◽  
Immunocompetent Cells ◽  
Mononuclear Leukocytes ◽  
Nuclear Transcription Factor ◽  
Stat Signaling ◽  
Increased Activity

Цель - изучение влияния тимозина 1 альфа на состояние внутриклеточных сигнальных механизмов, в частности, на состояние терминальных компонентов MAPK/SAPK и JAK/STAT-сигнальных путей в мононуклеарных лейкоцитах периферической крови у пациентов с артериальной гипертензией. Методика. Методом иммуноферментного анализа в мононуклеарных клетках пациентов определяли уровень фосфорилирования факторов STAT5A, STAT6, ERK1/2, p38, а также содержание ядерного фактора транскрипции NF-κB. Взаимосвязи между исследованными факторами оценивали методом линейного регрессионного анализа. Критериями включения в исследование являлись: возраст 45-55 лет, информированное согласие на участие в исследовании, окружность талии более 80 см у женщин и более 94 см у мужчин, артериальная гипертензия (АД ≥ 140/90 мм рт. ст.), а также уровень С-реактивного белка в сыворотке крови, определяемого высокочувствительным методом, в пределах ≥ 2,5 и <5,0 мг/дл), отсутствие в течение предшествующих 3 мес госпитализации, острых бактериальных и вирусных инфекций. Критериями исключения из исследования являлись обострения воспалительных заболеваний внутренних органов, декомпенсация углеводного обмена, отказ от участия в исследовании. Результаты. Повышение сывороточной концентрации Тα1 ассоциируется с активацией в мононуклеарных клетках факторов STAT5A, STAT6, а также протеинкиназ ERK и p38 и ядерного фактора транскрипции NF-κB. Высокая концентрация Тα1 ассоциировалась с повышением активности ядерного фактора транскрипции NF-κB, STAT6 и ERK. На этом фоне повышенный уровень продукции Тα1 сопровождался усилением активности факторов STAT6, STAT5A, а также протеинкиназ ERK и р38, не влияя при этом на активность NF-κB. Заключение. В физиологических концентрациях (0,9-2,85 пг/мл) Тα1 является иммуномодулятором, регулирующим активность MAPK/SAPK и JAK/STAT сигнальных путей через изменение реактивности иммунокомпетентных клеток к сигналам цитокинов, факторов роста и гормонам, в том числе, лептину, инсулину, соматотропину, не обладая при этом прямым активирующим влиянием на продукцию цитокинов. Полученные результаты позволяют рассматривать Тα1 в качестве иммунотропного регулятора, потенциальные эффекты которого (иммуномодулирующие, либо противовоспалительные) определяются его концентрацией в сыворотке, способствуя либо ограничению, либо прогрессированию иммунометаболических нарушений, лежащих в основе патогенеза атеросклероза и артериальной гипертонии.The aim of this work was to study effects of thymosin 1 alpha on intracellular signaling mechanisms, specifically, the state of terminal components of MAPK/SAPK and JAK/STAT signaling pathways in peripheral blood mononuclear leukocytes of patients with arterial hypertension. Methods. The level of phosphorylation of factors STAT5A, STAT6, ERK1/2, and p38 and the content of the nuclear transcription factor NF-κB were measured using the enzyme immunoassay. Relationship between the studied factors was assessed by the linear regression analysis. Results. The increase in serum Tα1 concentration was associated with activation of STAT5A and STAT6 as well as ERK and p38 protein kinases and the nuclear transcription factor NF-κB in mononuclear cells. A high concentration of Tα1 was associated with increased activity of the nuclear transcription factor NF-κB, STAT6, and ERK. In this process, the increased production of Tα1 was associated with increased activity of STAT6 and STAT5A as well as ERK and p38 protein kinases but with unchanged activity of NF-κB. Conclusion. At physiological concentrations (0.9-2.85 pg/ml), Tα1 is an important immunomodulator that regulates activities of the MAPK SAPK and JAK/STAT signaling pathways, thereby changing responses of immunocompetent cells to signals of cytokines, growth factors, and hormones, including leptin, insulin, and somatotropin without a direct activating effect on cytokine production by immunocompetent cells. The results of the study suggested that Tα1 is an immunomodulator potentially capable of correcting respective immunometabolic disorders in patients with hypertension.

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