scholarly journals Inhibiting MAPK14 showed anti-prolactinoma effect

2020 ◽  
Author(s):  
Qiaoyan Ding ◽  
Yu Zhang ◽  
Li Ma ◽  
Yong-gang Chen ◽  
Jin-hu Wu ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Gh3 Cells ◽  
Immunofluorescence Analysis ◽  
Mitogen Activated Protein ◽  
P38α Mapk ◽  
Interfering Rna

Abstract Background The specific underlying pathogenesis of prolactinoma has not been clarified yet, to the best of our knowledge. p38 mitogen-activated protein kinase (MAPK) signaling including p38α MAPK (MAPK14), p38β (MAPK11), p38γ (MAPK12) and p38δ (MAPK13) is associated with the development and progression of several types of cancer.Methods Immunofluorescence analysis was performed on the prolactin (PRL) and MAPK14 expressions of pituitary gland in C57BL/6 mice and human prolactinoma specimen. In the present study, the role of MAPK14 in prolactinoma was determined using estradiol-induced mice and dopamine D2 receptor knockout (DRD2-/-) mice models in C57BL/6 wild-type (WT), MAPK14-/- and DRD2-/-MAPK14+/- mice. GH3 cells were transfected with different sets of MAPK14 small interfering RNA, which to study MAPK14 and PRL expression in GH3 cells.Results Immunofluorescence analysis showed that PRL and MAPK14 expression were colocalized and increased in the pituitary gland of mice and human prolactinoma specimen compared with the control specimen. It was shown that PRL and MAPK14 expression was colocalized and increased significantly in the pituitary gland of estradiol-injected prolactinoma mice compared with the control mice. Knockout of MAPK14 significantly inhibited tumor overgrowth, and PRL expression was decreased in estradiol-induced mice. Furthermore, MAPK14 knockout of DRD2-/-MAPK14+/- mice significantly reduced the overgrowth of pituitary gland and PRL production and secretion compared with DRD2-/- mice. MAPK14 knockout using siRNA inhibited PRL production in GH3 cells.Conclusion These results suggest that MAPK14 serves a promoting role in the formation of prolactinoma, and highlights the potential of MAPK14 as a potential therapeutic target in the treatment of prolactinoma.

scholarly journals Inhibiting MAPK14 showed anti-prolactinoma effect

2020 ◽  
Author(s):  
Qiaoyan Ding ◽  
Yu Zhang ◽  
Li Ma ◽  
Yong-gang Chen ◽  
Jin-hu Wu ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Gh3 Cells ◽  
Immunofluorescence Analysis ◽  
Mitogen Activated Protein ◽  
P38α Mapk ◽  
Interfering Rna

Abstract Background The specific underlying pathogenesis of prolactinoma has not been clarified yet, to the best of our knowledge. p38 mitogen-activated protein kinase (MAPK) signaling including p38α MAPK (MAPK14), p38β (MAPK11), p38γ (MAPK12) and p38δ (MAPK13) is associated with the development and progression of several types of cancer.Methods Immunofluorescence analysis was performed on the prolactin (PRL) and MAPK14 expressions of pituitary gland in C57BL/6 mice and human prolactinoma specimen. In the present study, the role of MAPK14 in prolactinoma was determined using estradiol-induced mice and dopamine D2 receptor knockout (DRD2-/-) mice models in C57BL/6 wild-type (WT), MAPK14-/- and DRD2-/-MAPK14+/- mice. GH3 cells were transfected with different sets of MAPK14 small interfering RNA, which to study MAPK14 and PRL expression in GH3 cells.Results Immunofluorescence analysis showed that PRL and MAPK14 expression were colocalized and increased in the pituitary gland of mice and human prolactinoma specimen compared with the control specimen. It was shown that PRL and MAPK14 expression was colocalized and increased significantly in the pituitary gland of estradiol-injected prolactinoma mice compared with the control mice. Knockout of MAPK14 significantly inhibited tumor overgrowth, and PRL expression was decreased in estradiol-induced mice. Furthermore, MAPK14 knockout of DRD2-/-MAPK14+/- mice significantly reduced the overgrowth of pituitary gland and PRL production and secretion compared with DRD2-/- mice. MAPK14 knockout using siRNA inhibited PRL production in GH3 cells.Conclusion These results suggest that MAPK14 serves a promoting role in the formation of prolactinoma, and highlights the potential of MAPK14 as a potential therapeutic target in the treatment of prolactinoma.

scholarly journals Inhibiting MAPK14 showed anti-prolactinoma effect

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Qiao-yan Ding ◽  
Yu Zhang ◽  
Li Ma ◽  
Yong-gang Chen ◽  
Jin-hu Wu ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Gh3 Cells ◽  
Immunofluorescence Analysis ◽  
Mitogen Activated Protein ◽  
P38α Mapk ◽  
Interfering Rna

Abstract Background The specific underlying pathogenesis of prolactinoma has not been clarified yet, to the best of our knowledge. p38 mitogen-activated protein kinase (MAPK) signaling including p38α MAPK (MAPK14), p38β (MAPK11), p38γ (MAPK12) and p38δ (MAPK13) is associated with the development and progression of several types of cancer. Methods Immunofluorescence analysis was performed on the prolactin (PRL) and MAPK14 expressions of pituitary gland in C57BL/6 mice and human prolactinoma specimen. In the present study, the role of MAPK14 in prolactinoma was determined using estradiol-induced mice and dopamine D2 receptor knockout (DRD2−/−) mice models in C57BL/6 wild-type (WT), MAPK14−/− and DRD2−/−MAPK14+/− mice. GH3 cells were transfected with different sets of MAPK14 small interfering RNA, which to study MAPK14 and PRL expression in GH3 cells. Results Immunofluorescence analysis showed that PRL and MAPK14 expression were colocalized and increased in the pituitary gland of mice and human prolactinoma specimen compared with the control specimen. It was shown that PRL and MAPK14 expression was colocalized and increased significantly in the pituitary gland of estradiol-injected prolactinoma mice compared with the control mice. Knockout of MAPK14 significantly inhibited tumor overgrowth, and PRL expression was decreased in estradiol-induced mice. Furthermore, MAPK14 knockout of DRD2−/−MAPK14+/− mice significantly reduced the overgrowth of pituitary gland and PRL production and secretion compared with DRD2−/− mice. MAPK14 knockout using siRNA inhibited PRL production in GH3 cells. Conclusion These results suggest that MAPK14 serves a promoting role in the formation of prolactinoma, and highlights the potential of MAPK14 as a potential therapeutic target in the treatment of prolactinoma.

scholarly journals p38 MAPK α and β isoforms differentially regulate plasma membrane localization of MRP2

2016 ◽  
Vol 310 (11) ◽  
pp. G999-G1005 ◽  
Author(s):  
Christopher M. Schonhoff ◽  
Se Won Park ◽  
Cynthia R.L. Webster ◽  
M. Sawkat Anwer
Keyword(s):  
Plasma Membrane ◽  
P38 Mapk ◽  
Hepatoma Cell ◽  
Sodium Taurocholate ◽  
Mitogen Activated Protein Kinase ◽  
Hepatoma Cell Line ◽  
Mitogen Activated Protein ◽  
P38α Mapk ◽  
Opposing Effects ◽  
Interfering Rna

In hepatocytes, cAMP both activates p38 mitogen-activated protein kinase (MAPK) and increases the amount of multidrug resistance-associated protein-2 (MRP2) in the plasma membrane (PM-MRP2). Paradoxically, taurolithocholate (TLC) activates p38 MAPK but decreases PM-MRP2 in hepatocytes. These opposing effects of cAMP and TLC could be mediated via different p38 MAPK isoforms (α and β) that are activated differentially by upstream kinases (MKK3, MKK4, and MKK6). Thus we tested the hypothesis that p38α MAPK and p38β MAPK mediate increases and decreases in PM-MRP2 by cAMP and TLC, respectively. Studies were conducted in hepatocytes isolated from C57BL/6 wild-type (WT) and MKK3-knockout (MKK3−/−) mice and in a hepatoma cell line (HuH7) that overexpresses sodium-taurocholate cotransporting polypeptide (NTCP) (HuH-NTCP). Cyclic AMP activated MKK3, p38 MAPK, and p38α MAPK and increased PM-MRP2 in WT hepatocytes, but failed to activate p38α MAPK or increase PM-MRP2 in MKK3−/− hepatocytes. In contrast to cAMP, TLC activated total p38 MAPK but decreased PM-MRP2, and did not activate MKK3 or p38α MAPK in WT hepatocytes. In MKK3−/− hepatocytes, TLC still decreased PM-MRP2 and activated p38 MAPK, indicating that these effects are not MKK3-dependent. Additionally, TLC activated MKK6 in MKK3−/− hepatocytes, and small interfering RNA knockdown of p38β MAPK abrogated TLC-mediated decreases in PM-MRP2 in HuH-NTCP cells. Taken together, these results suggest that p38α MAPK facilitates plasma membrane insertion of MRP2 by cAMP, whereas p38β MAPK mediates retrieval of PM-MRP2 by TLC.

scholarly journals Inhibiting MAPK14 showed anti-prolactinomas effect

2020 ◽  
Author(s):  
Qiaoyan Ding ◽  
Yu Zhang ◽  
Li Ma ◽  
Yong-gang Chen ◽  
Jin-hu Wu ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Therapeutic Target ◽  
Mapk Signaling ◽  
Immunofluorescence Assay ◽  
Gh3 Cells ◽  
Wild Type ◽  
Potential Therapeutic Target ◽  
Protein Expressions ◽  
P38α Mapk

Abstract Background The pathogenesis of prolactinomas has not been clarified yet. p38 MAPK signaling including p38α MAPK (MAPK14), p38β (MAPK11), p38γ (MAPK12) and p38δ (MAPK13) is related to the development and progression of many cancers. We sought to investigate the role of MAPK14 in prolactinomas.Methods Immunofluorescence assay was performed on the prolactin (PRL) and MAPK14 protein expressions of pituitary gland in C57BL/6 mice and human prolactinomas specimens. We analyzed the role of MAPK14 in prolactinomas using estradiol-induced model and DRD2-/- model in C57BL/6 wild-type (WT), MAPK14-/- , DRD2-/-MAPK14+/- mice. GH3 cells were transfected with different sets of MAPK14 siRNA, which to study MAPK14 and PRL protein expression in GH3.Results Immunofluorescenc assaye found that PRL and MAPK14 were co-locatied and increased significantly in the pituitary gland of estradiol-injected prolactinomas mice than in control mice. And the deficiency of MAPK14 significantly inhibited the tumor overgrowth, along with the PRL decrease in estradiol-induced mice. Furthermore, MAPK14 deficiency in DRD2-/-MAPK14+/- mice significantly inhibited the overgrowth of pituitary gland and PRL production and secretion than in DRD2-/- mice. And MAPK14 knockdown by siRNA inhibited PRL production in GH3 cells.Conclusion The results establish that MAPK14 plays a promoting role in the formation of prolactinomas, and validate MAPK14 as potential therapeutic target.

scholarly journals Antiprolactinoma Effect of Hordenine by Inhibiting MAPK Signaling Pathway Activation in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Xiong Wang ◽  
Run-zhu Guo ◽  
Li Ma ◽  
Qiao-yan Ding ◽  
Jun-hua Meng ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Signaling Pathway ◽  
Mapk Pathway ◽  
Interleukin 1 ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Pathway Activation ◽  
Mitogen Activated Protein ◽  
Jnk Activation

Prolactinomas are harmful to human health, and the clinical first-line treatment drug is bromocriptine. However, 20% prolactinomas patients did not respond to bromocriptine. Hordenine is an alkaloid separated from Fructus Hordei Germinatus, which showed significant antihyperprolactinemia activity in rats. The aim of this study was to explore the effect and mechanism of hordenine on prolactinomas in rats. The study used estradiol to induce prolactinomas, which caused the activation of the pituitary mitogen-activated protein kinase (MAPK) pathway in rats significantly. The treatment of hordenine restored estradiol, induced the overgrowth of pituitary gland, and reduced the prolactin (PRL) accumulation in the serum and pituitary gland of rats by blocking the MAPK (p38, ERK1/2, and JNK) activation and production of inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). The antiprolactinoma effect of hordenine was mediated by inhibiting the MAPK signaling pathway activation in rats.

scholarly journals Specific Functional Features of the Cell Integrity MAP Kinase Pathway in the Dimorphic Fission Yeast Schizosaccharomyces japonicus

2021 ◽  
Vol 7 (6) ◽  
pp. 482
Author(s):  
Elisa Gómez-Gil ◽  
Alejandro Franco ◽  
Beatriz Vázquez-Marín ◽  
Francisco Prieto-Ruiz ◽  
Armando Pérez-Díaz ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Environmental Changes ◽  
Yeast Species ◽  
Mapk Signaling ◽  
Fine Tuning ◽  
Mitogen Activated Protein Kinase ◽  
Major Influence ◽  
Cell Integrity ◽  
Mitogen Activated Protein ◽  
Functional Features

Mitogen activated protein kinase (MAPK) signaling pathways execute essential functions in eukaryotic organisms by transducing extracellular stimuli into adaptive cellular responses. In the fission yeast model Schizosaccharomyces pombe the cell integrity pathway (CIP) and its core effector, MAPK Pmk1, play a key role during regulation of cell integrity, cytokinesis, and ionic homeostasis. Schizosaccharomyces japonicus, another fission yeast species, shows remarkable differences with respect to S. pombe, including a robust yeast to hyphae dimorphism in response to environmental changes. We show that the CIP MAPK module architecture and its upstream regulators, PKC orthologs Pck1 and Pck2, are conserved in both fission yeast species. However, some of S. pombe’s CIP-related functions, such as cytokinetic control and response to glucose availability, are regulated differently in S. japonicus. Moreover, Pck1 and Pck2 antagonistically regulate S. japonicus hyphal differentiation through fine-tuning of Pmk1 activity. Chimeric MAPK-swapping experiments revealed that S. japonicus Pmk1 is fully functional in S. pombe, whereas S. pombe Pmk1 shows a limited ability to execute CIP functions and promote S. japonicus mycelial development. Our findings also suggest that a modified N-lobe domain secondary structure within S. japonicus Pmk1 has a major influence on the CIP signaling features of this evolutionarily diverged fission yeast.

scholarly journals Effect of Static Magnetic Field on Monascus ruber M7 Based on Transcriptome Analysis

2021 ◽  
Vol 7 (4) ◽  
pp. 256
Author(s):  
Shuyan Yang ◽  
Hongyi Zhou ◽  
Weihua Dai ◽  
Juan Xiong ◽  
Fusheng Chen
Keyword(s):  
Magnetic Field ◽  
Static Magnetic Field ◽  
Morphological Characteristics ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Primary Metabolism ◽  
Monascus Ruber ◽  
Growing Period ◽  
Monascus Pigments ◽  
Mitogen Activated Protein

The effects of a static magnetic field (SMF) on Monascus ruber M7 (M. ruber M7) cultured on potato dextrose agar (PDA) plates under SMF treatment at different intensities (5, 10, and 30 mT) were investigated in this paper. The results revealed that, compared with the control (CK, no SMF treatment), the SMF at all tested intensities did not significantly influence the morphological characteristics of M. ruber M7, while the intracellular and extracellular Monascus pigments (MPs) and extracellular citrinin (CIT) of M. ruber M7 were increased at 10 and 30 mT SMF but there was no impact on the MPs and CIT at 5 mT SMF. The transcriptome data of M. ruber M7 cultured at 30 mT SMF on PDA for 3 and 7 d showed that the SMF could increase the transcriptional levels of some relative genes with the primary metabolism, including the carbohydrate metabolism, amino acid metabolism, and lipid metabolism, especially in the early growing period (3 d). SMF could also affect the transcriptional levels of the related genes to the biosynthetic pathways of MPs, CIT, and ergosterol, and improve the transcription of the relative genes in the mitogen-activated protein kinase (MAPK) signaling pathway of M. ruber M7. These findings provide insights into a comprehensive understanding of the effects of SMF on filamentous fungi.

scholarly journals The Emerging Role of Macrophages in Immune System Dysfunction under Real and Simulated Microgravity Conditions

2021 ◽  
Vol 22 (5) ◽  
pp. 2333
Author(s):  
Yulong Sun ◽  
Yuanyuan Kuang ◽  
Zhuo Zuo
Keyword(s):  
Immune System ◽  
Mapk Signaling ◽  
Immune Defense ◽  
Mitogen Activated Protein Kinase ◽  
Therapeutic Drugs ◽  
Physiological Processes ◽  
Immune System Dysfunction ◽  
Cell Immunity ◽  
Mitogen Activated Protein ◽  
Microgravity Conditions

In the process of exploring space, the astronaut’s body undergoes a series of physiological changes. At the level of cellular behavior, microgravity causes significant alterations, including bone loss, muscle atrophy, and cardiovascular deconditioning. At the level of gene expression, microgravity changes the expression of cytokines in many physiological processes, such as cell immunity, proliferation, and differentiation. At the level of signaling pathways, the mitogen-activated protein kinase (MAPK) signaling pathway participates in microgravity-induced immune malfunction. However, the mechanisms of these changes have not been fully elucidated. Recent studies suggest that the malfunction of macrophages is an important breakthrough for immune disorders in microgravity. As the first line of immune defense, macrophages play an essential role in maintaining homeostasis. They activate specific immune responses and participate in large numbers of physiological activities by presenting antigen and secreting cytokines. The purpose of this review is to summarize recent advances on the dysfunction of macrophages arisen from microgravity and to discuss the mechanisms of these abnormal responses. Hopefully, our work will contribute not only to the future exploration on the immune system in space, but also to the development of preventive and therapeutic drugs against the physiological consequences of spaceflight.

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