scholarly journals Thyrotropin-Releasing Hormone-Stimulated Thyrotropin Expression Involves Islet-Brain-1/c-Jun N-Terminal Kinase Interacting Protein-1

Endocrinology ◽  
2004 ◽  
Vol 145 (12) ◽  
pp. 5623-5628 ◽  
Author(s):  
Hiroshi Abe ◽  
Koji Murao ◽  
Hitomi Imachi ◽  
Wen M. Cao ◽  
Xiao Yu ◽  
...  
Keyword(s):  
Potential Role ◽  
Endocrine Pancreas ◽  
Transient Transfection ◽  
Gh3 Cells ◽  
Gene Encoding ◽  
Interacting Protein ◽  
Protein Levels ◽  
Stimulation Of ◽  
Transfection Study

Abstract Islet-brain-1 (IB1)/c-Jun N-terminal kinase interacting protein 1 (JIP-1) is a scaffold protein that is expressed at high levels in neurons and the endocrine pancreas. IB1/JIP-1 interacts with the c-Jun N-terminal kinase and mediates the specific physiological stimuli (such as cytokines). However, the potential role of the protein in the pituitary has not been evaluated. Herein, we examined expression of the gene encoding IB1/JIP-1 and its translated product in the anterior pituitary gland and a pituitary cell line, GH3. We then examined the potential role of IB1/JIP-1 in controlling TSH-β gene expression. Exposure of GH3 cells to TRH stimulated the expression of IB1/JIP-1 protein levels, mRNA, and transcription of the promoter. The increase of IB1/JIP-1 content by transient transfection study of a vector encoding IB1/JIP-1 or by the stimulation of TRH stimulates TSH-β promoter activity. This effect is not found in the presence of a mutated nonfunctional (IB1S59N) IB1/JIP-1 protein. Together, these facts point to a central role of the IB1/JIP-1 protein in the control of TRH-mediated TSH-β stimulation.

scholarly journals The Role of Interleukin-23 in the Early Development of Emphysema in HIV1+Smokers

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Igor Z. Barjaktarevic ◽  
Ronald G. Crystal ◽  
Robert J. Kaner
Keyword(s):  
Tissue Destruction ◽  
Epithelial Lining Fluid ◽  
Protein Levels ◽  
Knowing That ◽  
Lung Epithelial ◽  
Interleukin 23 ◽  
Metalloproteinase 9 ◽  
Stimulation Of

Rationale.Matrix metalloproteinase-9 (MMP-9) expression is upregulated in alveolar macrophages (AM) of HIV1+smokers who develop emphysema. Knowing that lung epithelial lining fluid (ELF) of HIV1+smokers contains increased levels of inflammatory cytokines compared to HIV1−smokers, we hypothesized that upregulation of lung cytokines in HIV1+smokers may be functionally related to increased MMP-9 expression.Methods.Cytokine arrays evaluated cytokine protein levels in ELF obtained from 5 groups of individuals: HIV1−healthy nonsmokers, HIV1−healthy smokers, HIV1−smokers with low diffusing capacity (DLCO), HIV1+nonsmokers, and HIV1+smokers with lowDLCO.Results. Increased levels of the Th17 related cytokine IL-23 were found in HIV1−smokers with lowDLCOand HIV1+smokers and nonsmokers. Relative IL-23 gene expression was increased in AM of HIV1+individuals, with greater expression in AM of HIV1+smokers with lowDLCO. Infection with HIV1in vitroinduced IL-23 expression in normal AM. IL-23 stimulation of AM/lymphocyte coculturesin vitroinduced upregulation of MMP-9. Lung T lymphocytes express receptor IL-23R and interact with AM in order to upregulate MMP-9.Conclusion. This mechanism may contribute to the increased tissue destruction in the lungs of HIV1+smokers and suggests that Th17 related inflammation may play a role.

scholarly journals Polyamines regulate gene expression by stimulating translation of histone acetyltransferase mRNAs

2020 ◽  
Vol 295 (26) ◽  
pp. 8736-8745 ◽  
Author(s):  
Akihiko Sakamoto ◽  
Yusuke Terui ◽  
Takeshi Uemura ◽  
Kazuei Igarashi ◽  
Keiko Kashiwagi
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Histone Acetyltransferases ◽  
Regulate Gene Expression ◽  
Double Stranded Rna ◽  
Protein Levels ◽  
Lysine Residues ◽  
Regulate Gene ◽  
Stimulation Of

Polyamines regulate gene expression in Escherichia coli by translationally stimulating mRNAs encoding global transcription factors. In this study, we focused on histone acetylation, one of the mechanisms of epigenetic regulation of gene expression, to attempt to clarify the role of polyamines in the regulation of gene expression in eukaryotes. We found that activities of histone acetyltransferases in both the nucleus and cytoplasm decreased significantly in polyamine-reduced mouse mammary carcinoma FM3A cells. Although protein levels of histones H3 and H4 did not change in control and polyamine-reduced cells, acetylation of histones H3 and H4 was greatly decreased in the polyamine-reduced cells. Next, we used control and polyamine-reduced cells to identify histone acetyltransferases whose synthesis is stimulated by polyamines. We found that polyamines stimulate the translation of histone acetyltransferases GCN5 and HAT1. Accordingly, GCN5- and HAT1-catalyzed acetylation of specific lysine residues on histones H3 and H4 was stimulated by polyamines. Consistent with these findings, transcription of genes required for cell proliferation was enhanced by polyamines. These results indicate that polyamines regulate gene expression by enhancing the expression of the histone acetyltransferases GCN5 and HAT1 at the level of translation. Mechanistically, polyamines enhanced the interaction of microRNA-7648-5p (miR-7648-5p) with the 5′-UTR of GCN5 mRNA, resulting in stimulation of translation due to the destabilization of the double-stranded RNA (dsRNA) between the 5′-UTR and the ORF of GCN5 mRNA. Because HAT1 mRNA has a short 5′-UTR, polyamines may enhance initiation complex formation directly on this mRNA.

scholarly journals The Role of RUNX2 in Osteosarcoma Oncogenesis

Sarcoma ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
J. W. Martin ◽  
M. Zielenska ◽  
G. S. Stein ◽  
A. J. van Wijnen ◽  
J. A. Squire
Keyword(s):  
Cellular Differentiation ◽  
Cell Cycle Progression ◽  
Potential Role ◽  
Breast Cancers ◽  
Cycle Progression ◽  
Protein Levels ◽  
Biological Heterogeneity ◽  
Runx Proteins ◽  
Osteoblast Maturation

Osteosarcoma is an aggressive but ill-understood cancer of bone that predominantly affects adolescents. Its rarity and biological heterogeneity have limited studies of its molecular basis. In recent years, an important role has emerged for the RUNX2 “platform protein” in osteosarcoma oncogenesis. RUNX proteins are DNA-binding transcription factors that regulate the expression of multiple genes involved in cellular differentiation and cell-cycle progression. RUNX2 is genetically essential for developing bone and osteoblast maturation. Studies of osteosarcoma tumours have revealed that the RUNX2 DNA copy number together with RNA and protein levels are highly elevated in osteosarcoma tumors. The protein is also important for metastatic bone disease of prostate and breast cancers, while RUNX2 may have both tumor suppressive and oncogenic roles in bone morphogenesis. This paper provides a synopsis of the current understanding of the functions of RUNX2 and its potential role in osteosarcoma and suggests directions for future study.

Potential role of antibodies against cardiac Kv channel-interacting protein 2 in dilated cardiomyopathy

2008 ◽  
Vol 156 (1) ◽  
pp. 92-99.e2 ◽  
Author(s):  
Martin Landsberger ◽  
Alexander Staudt ◽  
Sangita Choudhury ◽  
Christiane Trimpert ◽  
Lars R. Herda ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Potential Role ◽  
Interacting Protein ◽  
Kv Channel

scholarly journals Endothelin in health and disease

2004 ◽  
Vol 4 (3) ◽  
pp. 31-34 ◽  
Author(s):  
Emina Nakaš-Ićindić ◽  
Asija Začiragić ◽  
Almira Hadžović ◽  
Nešina Avdagić
Keyword(s):  
Nitric Oxide ◽  
Amino Acids ◽  
Calcium Ions ◽  
Potential Role ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Health And Disease ◽  
Endothelin 3 ◽  
Stimulation Of

Endothelin is a recently discovered peptide composed of 21 amino acids. There are three endothelin isomers: endothelin -1 (ET-1), endothelin -2 (ET-2) and endothelin - 3 (ET-3). In humans and animals levels of ET-1, ET-2, ET-3 and big endothelin in blood range from 0,3 to 3 pg/ml. ET-1, ET-2 and ET-3 act by binding to receptors. Two main types of the receptors for endothelins exist and they are referred to as A and B type receptors. Different factors can stimulate or inhibit production of endothelin by endothelial cells. Mechanical stimulation of endothehum, thrombin, calcium ions, epinephrine, angiotensin II, vasopressin, dopamine, cytokines, growth factors stimulate the production of endothelin whereas nitric oxide, cyclic guanosine monophosphate, atrial natriuretic peptide, prostacyclin, bradykinin inhibit its production. Endothelins have different physiological roles in human body but at the same time their actions are involved in the pathogenesis of many diseases.The aim of this review was to present some of, so far, the best studied physiological roles of endothelin and to summarize evidence supporting the potential role of ET in the pathogenesis of certain diseases.

scholarly journals DsbA-L protects against diabetic renal injury through the adipo-renal axis

2021 ◽  
Author(s):  
Lingfeng Zeng ◽  
Ming Yang ◽  
Chun Hu ◽  
Li Zhao ◽  
Xianghui Chen ◽  
...  
Keyword(s):  
Renal Injury ◽  
Kidney Tissue ◽  
Normal Control Group ◽  
Control Group ◽  
Diabetic Mice ◽  
Urine Protein ◽  
Interacting Protein ◽  
Protein Levels ◽  
Mrna And Protein Expression

AbstractDisulfide-bond A oxidoreductase-like protein (DsbA-L) is an adiponectin-interacting protein that is highly expressed in adipose tissue. The adipo-renal axis involves adipocyte release of signaling molecules that are recruited to kidney and regulate kidney function. We have found that the DsbA-L modulated the progression of diabetic nephropathy, but the precise mechanism of this modulation is unknown. Here, the transgenic mice overexpressing DsbA-L protein in fat (fDsbA-L) were used to verify that the renoprotective role of DsbA-L whether by adipo-renal axis. Mice were divided into four groups: a normal (Control) group, STZ induced diabetic mice, fDsbA-L mice and diabetic fDsbA-L mice (n=6). Diabetes was induced in mice by STZ 100mg/kg and continued HFD feeding for 12 weeks. Compared with the control group, the weight, blood glucose,and urine protein levels and the pathological changes in the kidney tissue of diabetic mice were increased significantly, accompanied by increased NLRP3,caspase-1, IL-1β, IL-18, FN, and Collagen1 mRNA and protein expression, which were reduced in diabetic fDsbA-L mice. Interestingly, the level of adiponectin in serum and kidney expression in diabetic mice was reduced significantly compared to that in the control group. However this change was reversed in diabetic fDsbA-L mice. These data suggest that the overexpression of DsbA-L in the adipocytes of mice can protect against diabetic renal injury through anti-inflammatory mediators,and may be mediated by the adipo-renal axis.

scholarly journals The Presence and Potential Role of ALDH1A2 in the Glioblastoma Microenvironment

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2485
Author(s):  
Stephanie Sanders ◽  
Denise M. Herpai ◽  
Analiz Rodriguez ◽  
Yue Huang ◽  
Jeff Chou ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Potential Role ◽  
Therapeutic Agents ◽  
Brain Parenchyma ◽  
Low Grade ◽  
Effective Management ◽  
Diffuse Infiltration ◽  
Protein Levels ◽  
The Brain

Glioblastoma (GBM) is the most aggressive malignant glioma. Therapeutic targeting of GBM is made more difficult due to its heterogeneity, resistance to treatment, and diffuse infiltration into the brain parenchyma. Better understanding of the tumor microenvironment should aid in finding more effective management of GBM. GBM-associated macrophages (GAM) comprise up to 30% of the GBM microenvironment. Therefore, exploration of GAM activity/function and their specific markers are important for developing new therapeutic agents. In this study, we identified and evaluated the expression of ALDH1A2 in the GBM microenvironment, and especially in M2 GAM, though it is also expressed in reactive astrocytes and multinucleated tumor cells. We demonstrated that M2 GAM highly express ALDH1A2 when compared to other ALDH1 family proteins. Additionally, GBM samples showed higher expression of ALDH1A2 when compared to low-grade gliomas (LGG), and this expression was increased upon tumor recurrence both at the gene and protein levels. We demonstrated that the enzymatic product of ALDH1A2, retinoic acid (RA), modulated the expression and activity of MMP-2 and MMP-9 in macrophages, but not in GBM tumor cells. Thus, the expression of ALDH1A2 may promote the progressive phenotype of GBM.

scholarly journals Fyn kinase–tubulin interaction during meiosis of rat eggs

Reproduction ◽  
2004 ◽  
Vol 128 (4) ◽  
pp. 387-393 ◽  
Author(s):  
A Talmor-Cohen ◽  
R Tomashov-Matar ◽  
W B Tsai ◽  
W H Kinsey ◽  
R Shalgi
Keyword(s):  
Potential Role ◽  
Active Form ◽  
Src Family Kinase ◽  
Fyn Kinase ◽  
Phase Arrest ◽  
Vertebrate Eggs ◽  
Rat Eggs ◽  
Stimulation Of

Prior to fertilization, the spindle of vertebrate eggs must remain stable and well organized during the second meiotic meta-phase arrest (MII). In a previous study we have determined that the completion of meiosis is a Src family kinase (SFK)-dependent event. In the current study we have used the SFK inhibitors, SU6656 and PP2, and demonstrated that inhibition of SFKs caused the formation of a disorganized spindle. The observation that proper organization of an MII spindle is an SFK-dependent process, combined with our previous finding that Fyn kinase is localized at the microtubules (MTs), prompted us to examine the potential role of Fyn in MT signaling. Our results show an association between Fyn and tubulin, the ability of Fyn to phosphorylate tubulinin vitroand stimulation of meiosis completion by injection of a constitutively active form of Fyn (CAF).We suggested that SFKs mediate significant functions during the organization of the MII spindle. In view of CAF injection experiments, and of the pronounced concentration of Fyn kinase at the spindle, we propose that Fyn may play an important role in some aspects of the spindle functions, possibly those involving the MTs.

scholarly journals TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy

2017 ◽  
Vol 114 (43) ◽  
pp. 11524-11529 ◽  
Author(s):  
Cheryl E. G. Leyns ◽  
Jason D. Ulrich ◽  
Mary B. Finn ◽  
Floy R. Stewart ◽  
Lauren J. Koscal ◽  
...  
Keyword(s):  
Microglial Activation ◽  
Potential Role ◽  
Piriform Cortex ◽  
Tau Pathology ◽  
Gene Encoding ◽  
Gene Expression Analyses ◽  
Unexpected Findings ◽  
Microglial Response ◽  
The Brain

Variants in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) were recently found to increase the risk for developing Alzheimer’s disease (AD). In the brain, TREM2 is predominately expressed on microglia, and its association with AD adds to increasing evidence implicating a role for the innate immune system in AD initiation and progression. Thus far, studies have found TREM2 is protective in the response to amyloid pathology while variants leading to a loss of TREM2 function impair microglial signaling and are deleterious. However, the potential role of TREM2 in the context of tau pathology has not yet been characterized. In this study, we crossed Trem2+/+ (T2+/+) and Trem2−/− (T2−/−) mice to the PS19 human tau transgenic line (PS) to investigate whether loss of TREM2 function affected tau pathology, the microglial response to tau pathology, or neurodegeneration. Strikingly, by 9 mo of age, T2−/−PS mice exhibited significantly less brain atrophy as quantified by ventricular enlargement and preserved cortical volume in the entorhinal and piriform regions compared with T2+/+PS mice. However, no TREM2-dependent differences were observed for phosphorylated tau staining or insoluble tau levels. Rather, T2−/−PS mice exhibited significantly reduced microgliosis in the hippocampus and piriform cortex compared with T2+/+PS mice. Gene expression analyses and immunostaining revealed microglial activation was significantly attenuated in T2−/−PS mice, and there were lower levels of inflammatory cytokines and astrogliosis. These unexpected findings suggest that impairing microglial TREM2 signaling reduces neuroinflammation and is protective against neurodegeneration in the setting of pure tauopathy.

scholarly journals Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Ken-ichiro Nakajima ◽  
Zhenzhong Cui ◽  
Chia Li ◽  
Jaroslawna Meister ◽  
Yinghong Cui ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Potential Role ◽  
G Protein Coupled Receptors ◽  
Signalling Cascades ◽  
Treatment Of Obesity ◽  
G Protein Coupled ◽  
Stimulation Of ◽  
Sustained Increase

Abstract Agouti-related peptide (AgRP) neurons of the hypothalamus play a key role in regulating food intake and body weight, by releasing three different orexigenic molecules: AgRP; GABA; and neuropeptide Y. AgRP neurons express various G protein-coupled receptors (GPCRs) with different coupling properties, including Gs-linked GPCRs. At present, the potential role of Gs-coupled GPCRs in regulating the activity of AgRP neurons remains unknown. Here we show that the activation of Gs-coupled receptors expressed by AgRP neurons leads to a robust and sustained increase in food intake. We also provide detailed mechanistic data linking the stimulation of this class of receptors to the observed feeding phenotype. Moreover, we show that this pathway is clearly distinct from other GPCR signalling cascades that are operative in AgRP neurons. Our data suggest that drugs able to inhibit this signalling pathway may become useful for the treatment of obesity.

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