scholarly journals Serotonin regulates maternal calcium homeostasis during the perinatal period of sheep

2019 ◽  
Vol 97 (12) ◽  
pp. 5009-5015
Author(s):  
Lu Jin ◽  
Nameiriga ◽  
Haizhou Sun ◽  
Sang Dan ◽  
Shengli Li ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Mrna Expression ◽  
Secretory Pathway ◽  
Nuclear Factor Kappa B ◽  
Total Serum ◽  
Saline Control ◽  
Control Group ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Parathyroid Hormone Related Protein

Abstract The goal of this experiment was to demonstrate the ability of an infusion of serotonin (5-HT; 5-hydroxytryptamine) precursors to increase 5-HT production during the transition from pregnancy to lactation and its effects on gene expression related to calcium (Ca) transporters in the mammary gland and bone resorption markers in the femur. Thirty pregnant Bamei mutton sheep were randomly assigned to 3 experimental groups. All groups received a daily intravenous infusion of saline (control group; n = 10), saline containing 0.178 mg of L-tryptophan/kg body weight (BW) (TRP group, n = 10) or 0.178 mg of 5-hydroxytryptophan/kg BW (5-HTP group, n = 10), beginning on day 7 of prepartum and continuing until delivery. Serum (pre- and postpartum), milk (postpartum), and femur and mammary gland tissue (day 9) were collected. Sheep infused with 5-HTP had a larger total serum Ca concentration on days 3, 6, 15, and 30 of lactation and total milk Ca concentration on days 3, 6, 12, and 15 of lactation compared with that of the control group. Sheep infused with 5-HTP and TRP increased blood and milk concentrations of 5-HT on days 3, 6, 9, and 30 of lactation and parathyroid hormone-related protein (PTHrP) on day 3 of prepartum and on days 3, 6, and 15 of lactation (P < 0.05). In addition, compared to that of the control group, the TRP or 5-HTP infusion upregulated PTHrP, a sodium/calcium exchanger, plasma membrane Ca2+ ATPase 2, secretory pathway Ca2+ ATPase 1, and calcium sensing receptor mRNA expression in mammary gland and receptor-activated nuclear factor kappa-B ligand mRNA expression in the femur, but had no effect on receptor-activated nuclear factor kappa-B and osteoprotegerin mRNA expression in the femur (P < 0.05). This suggests that 5-HT and PTHrP may be involved in regulating maternal Ca homeostasis during the transition from pregnancy to lactation in the sheep.

scholarly journals Time-Resolved Effect of Interferon-Alpha 2a on Activities of Nuclear Factor Kappa B, Pregnane X Receptor and on Drug Disposition Genes

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 808
Author(s):  
Dirk Theile ◽  
Lelia Wagner ◽  
Cindy Bay ◽  
Walter Emil Haefeli ◽  
Johanna Weiss
Keyword(s):  
Mrna Expression ◽  
Interferon Alpha ◽  
Nuclear Factor Kappa B ◽  
Drug Disposition ◽  
Pregnane X Receptor ◽  
Nuclear Factor ◽  
Cyp3a4 Activity ◽  
Time Resolved ◽  
Nuclear Factor Kappa ◽  
Disposition Genes

Interferon-alpha (IFN-α) is suggested to cause pharmacokinetic drug interactions by lowering expression of drug disposition genes through affecting the activities of nuclear factor kappa B (NF-ĸB) and pregnane X receptor (PXR). The time-resolved impact of IFN-α 2a (1000 U/mL; 5000 U/mL; 2 h to 30 h) on the activities of NF-ĸB and PXR and mRNA expression (5000 U/mL; 24 h, 48 h) of selected drug disposition genes and on cytochrome P450 (CYP3A4) activity in LS180 cells (5000 U/mL; 24 h, 48 h) was evaluated using luciferase-based reporter gene assays, reverse transcription polymerase chain reaction, and luminescence-based CYP3A4 activity assays. The cross-talk between NF-ĸB activation and PXR suppression was evaluated by NF-ĸB blockage (10 µM parthenolide). IFN-α 2a initially (2 h, 6 h) enhanced NF-ĸB activity 2-fold and suppressed PXR activity by 30%. mRNA of CYP3A4 was halved, whereas UGT1A1 was increased (1.35-fold) after 24 h. After 48 h, ABCB1 expression was increased (1.76-fold). CYP3A4 activity remained unchanged after 24 h, but was enhanced after 48 h (1.35-fold). IFN-α 2a demonstrated short-term suppressive effects on PXR activity and CYP3A4 mRNA expression, likely mediated by activated NF-ĸB. Longer exposure enhanced CYP3A4 activity. Clinical trials should evaluate the relevance by investigating the temporal effects of IFN-α on CYP3A4 using a sensitive marker substrate.

scholarly journals A20 of nucleus pulposus cells plays a self-protection role via the nuclear factor-kappa B pathway in the inflammatory microenvironment

2020 ◽  
Vol 9 (5) ◽  
pp. 225-235
Author(s):  
Xin Peng ◽  
Cong Zhang ◽  
Jun-Ping Bao ◽  
Lei Zhu ◽  
Rui Shi ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Messenger Rna ◽  
Nuclear Factor Kappa B ◽  
Intervertebral Discs ◽  
Control Group ◽  
Nuclear Factor ◽  
Nucleus Pulposus Cells ◽  
Necrosis Factor Alpha ◽  
Nuclear Factor Kappa ◽  
Tnf Α

Aims Inflammatory response plays a pivotal role in the pathophysiological process of intervertebral disc degeneration (IDD). A20 (also known as tumour necrosis factor alpha-induced protein 3 (TNFAIP3)) is a ubiquitin-editing enzyme that restricts nuclear factor-kappa B (NF-κB) signalling. A20 prevents the occurrence of multiple inflammatory diseases. However, the role of A20 in the initiation of IDD has not been elucidated. The aim of the study was to investigate the effect of A20 in senescence of TNF alpha (TNF-α)-induced nucleus pulposus cells (NPCs). Methods Immunohistochemical staining was performed to observe the expression of A20 in normal and degenerated human intervertebral discs. The NPCs were dissected from the tail vertebrae of healthy male Sprague-Dawley rats and were cultured in the incubator. In the experiment, TNF-α was used to mimic the inflammatory environment of IDD. The cell viability and senescence were examined to investigate the effect of A20 on TNF-α-treated NPCs. The expression of messenger RNA (mRNA)-encoding proteins related to matrix macromolecules (collagen II, aggrecan) and senescence markers (p53, p16). Additionally, NF-κB/p65 activity of NPCs was detected within different test compounds. Results The expression of A20 was upregulated in degenerate human intervertebral discs. The A20 levels of NPCs in TNF-α inflammatory microenvironments were dramatically higher than those of the control group. TNF-α significantly decreased cell proliferation potency but increased senescence-associated beta-galactosidase (SA-β-Gal) activity, the expression of senescence-associated proteins, the synthesis of extracellular matrix, and G1 cycle arrest. The senescence indicators and NF-κB/p65 expression of A20 downregulated group treated with TNF-α were significantly upregulated compared to TNF-α-treated normal NPCs. Conclusion A20 has a self-protective effect on the senescence of NPCs induced by TNF-α. The downregulation of A20 in NPCs exacerbated the senescence of NPCs induced by TNF-α. Cite this article: Bone Joint Res. 2020;9(5):225–235.

scholarly journals Biphasic Activation of Nuclear Factor-Kappa B in Experimental Models of Subarachnoid HemorrhageIn VivoandIn Vitro

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Wan-Chun You ◽  
Wei Li ◽  
Zong Zhuang ◽  
Yong Tang ◽  
Hu-Chen Lu ◽  
...  
Keyword(s):  
Nuclear Factor Kappa B ◽  
Experimental Models ◽  
Control Group ◽  
Cultured Neurons ◽  
Nuclear Factor ◽  
Gene Expressions ◽  
Mobility Shift ◽  
Nuclear Factor Kappa ◽  
Significant Difference ◽  
Mobility Shift Assay

It has been proven that nuclear factor-kappa B (NF-κB) is activated as a well-known transcription factor after subarachnoid hemorrhage (SAH). However, the panoramic view of NF-κB activity after SAH remained obscure. Cultured neurons were signed into control group and six hemoglobin- (Hb-) incubated groups. One-hemorrhage rabbit SAH model was produced, and the rabbits were divided randomly into one control group and five SAH groups. NF-κB activity was detected by electrophoretic mobility shift assay (EMSA) and immunohistochemistry. Real-time polymerase chain reaction (PCR) was performed to assess the downstream genes of NF-κB. NeuN immunofluorescence and lactate dehydrogenase (LDH) quantification were used to estimate the neuron injury. Double drastically elevated NF-κB activity peaks were detected in rabbit brains and cultured neurons. The downstream gene expressions showed an accordant phase peaks. NeuN-positive cells decreased significantly in day 3 and day 10 groups. LDH leakage exhibited a significant increase in Hb-incubated groups, but no significant difference was found between the Hb incubated groups. These results suggested that biphasic increasing of NF-κB activity was induced after SAH, and the early NF-κB activity peak indicated the injury role on neurons; however, the late peak might not be involved in the deteriorated effect on neurons.

scholarly journals The Long Noncoding RNA ANRIL Promotes Cell Apoptosis in Lipopolysaccharide-Induced Acute Kidney Injury Mediated by the TLR4/Nuclear Factor-Kappa B Pathway

2020 ◽  
Vol 45 (2) ◽  
pp. 209-221 ◽  
Author(s):  
Ye Zhu ◽  
Sheng-Wei Wei ◽  
Ao Ding ◽  
Wei-Ping Zhu ◽  
Mei-Fang Mai ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Nuclear Factor Kappa B ◽  
Quantitative Polymerase Chain Reaction ◽  
Kidney Tissue ◽  
Inflammatory Factors ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa

Background/Aims: The purpose of this study is to analyze the expression and biological function of lncRNA ANRIL, microRNA-199a, TLR4, and nuclear factor-kappa B (NF-κB) in acute renal injury (AKI) induced by lipopolysaccharide (LPS). Methods: The levels of ANRIL and microRNA-199a in mouse cells and kidneys were detected by quantitative-polymerase chain reaction. Western blot analysis was used for the NF-κB pathway protein. MTT assay was used for cell viability. Enzyme-linked immunosorbent assay was used for the secretion of inflammatory factors in mouse kidney tissue. Apoptosis was measured by flow cytometry and Western blotting. The potential binding region between ANRIL and miR-199a was verified by luciferase reporter assay. Results: The upregulation of ANRIL can reduce the expression of microRNA-199a and increases the number of apoptotic cells. The expression levels of ANRIL in LPS-induced AKI mice and LPS-treated HK2 cells were upregulated compared with the control group. Overexpression of ANRIL increased apoptosis and promoted TLR4 (Toll-like receptor 4), NF-κB phosphorylation, and downstream transcription factor production. Conclusion: ANRIL/NF-κB pathway in LPS-induced apoptosis provided theoretical guidance for ANRIL in the treatment of AKI.

126 NUCLEAR TRANSLOCATION OF NUCLEAR FACTOR KAPPA B AND ITS ROLE IN MOUSE PRE-IMPLANTATION DEVELOPMENT

2006 ◽  
Vol 18 (2) ◽  
pp. 172
Author(s):  
Y. Fumiiwa ◽  
H. Imai ◽  
M. Yamada
Keyword(s):  
Treatment Group ◽  
Nuclear Factor Kappa B ◽  
Nuclear Translocation ◽  
Blastocyst Stage ◽  
Control Group ◽  
Nuclear Factor ◽  
Cell Stage ◽  
Nuclear Factor Kappa ◽  
Morphological Aberration ◽  
The One

In mouse pre-implantation development, it has been reported that RelA, one of the subunits of nuclear factor kappa B (NF-�B), is expressed in eggs and embryos from the Metaphase II oocyte to the blastocyst stage. However, the role of NF-�B in the pre-implantation development has not yet been elucidated in detail. In this study, we examined (1) the activation of NF-�B during mouse pre-implantation development and (2) the effect of a synthetic peptide inhibitor of NF-�B, SN-50, which inhibits nuclear translocation of NF-�B on the pre-implantation development. Fertilized one-cell embryos were collected 17 h post-hCG from the ampullae of oviducts of superovulated ICR mouse females that had been mated with the same strain of males and then were cultured in KSOM medium at 37�C under 5% CO2 in air for 4 d. To elucidate the timing of NF-�B activation, we examined the localization of NF-�B in the nucleus by an immunofluorescence approach using RelA antibody with a laser confocal microscope. RelA was distributed mainly in the cytoplasm of embryos from the one-cell stage through the blastocyst stages. The presence of RelA in the nucleus, evidence for NF-�B activation, was observed in embryos from the one-cell to the compacted 8-cell stages. Moreover, we observed RelA punctate localization in nucleoplasm of embryos from the one-cell to the 4-cell stages, and nuclear dots were enriched conspicuously in the one-cell embryos and the late 2-cell embryos. These results suggest that NF-�B is activated in embryos from the one-cell to the compacted 8-cell stages and that its activation seems to be particularly strong at the developmental stage when RelA appeared to be concentrated in nuclear dots, as it has been reported that NF-�B and other transcription factors and co-activators form punctate structures called 'enhanceosom' in association with particular promoters in the nucleus. Next, we examined the effect of SN-50 on the pre-implantation development of mouse embryos. When embryos were treated with SN-50 at 20 �g/mL from the 2-cell stage, 63% (33 of 52) of the embryos developed to blastocysts, but 55% (18 of 33) of the blastocysts showed abnormal morphology, such as poor cavitation, and many degenerating cells extruded into the perivitelline space. The percentages of 2-cell embryos that formed morphologically normal blastocysts were significantly lower in the SN-50 treatment group (29%; 15 of 52) than in the untreated control group (76%; 35 of 46) and in the SN-50M (inactive analogue of SN-50, 20 �g/mL) treatment group (72%; 38 of 53). These experiments were done in 4 replicates, and the statistical analyses of the data were done by ANOVA and Fisher's PLSD test. Nuclear location of RelA was not observed in the embryos at the 4-cell stage when treated with SN-50 from the 2-cell stage, although observed in control and SN-50M-treated embryos. Furthermore, it was found that most of embryos (23 of 37) treated with SN-50 from the compacted 8-cell or morula stages developed normally to the blastocyst stage as control embryos (25 of 36). These results suggest that morphological aberration at the blastocyst stage is elicited by inhibiting NF-�B activation.

Baicalin Inhibits Kidney Inflammation in Mice with Diabetic Nephropathy by Modulating Toll-like Receptor 4/Nuclear Factor-Kappa B Signaling Pathway

2020 ◽  
Vol 19 (1) ◽  
pp. 115-119
Author(s):  
Benyong Wang ◽  
Ning Zhao ◽  
Pingyue Ma ◽  
Qunhong Xu ◽  
Qi Chen
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Nuclear Factor Kappa B ◽  
Kidney Tissue ◽  
Control Group ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Nuclear Factor Kappa ◽  
Factor Α

We have explored the effect of baicalin, an anti-inflammatory agent, on the outcome of diabetic nephropathy. To this end, we used 6 weeks old C57BL/6J male diabetic mice exhibiting nephropathy. The treatment with baicalin exhibited significant improvement in the renal function, histopathological changes, and expression of inflammatory markers. Moreover, the expression of interleukin-6, tumor necrosis factor-α, and interleukin-1β in kidney tissue of the mice in baicalin group were significantly downregulated compared to the control group (P ‹ 0.05). The expression of toll-like receptor 4, myeloid differentiation factor 88, and nuclear factor-kappa B proteins in the kidney of baicalin-treated mice were remarkably downregulated compared to the control group. Taken together, we conclude that baicalin may exert its protective effect on kidney by inhibiting inflammation through toll-like receptor 4/nuclear factor-kappa B signaling pathway in mice with diabetic nephropathy.

scholarly journals Do anti-carbamylated protein antibodies in rheumatoid arthritis reflect local and systemic osteoporosis? A study of osteoprotegrin and receptor activator for nuclear factor kappa B ligand and radiological assessment

2021 ◽  
Vol 48 (1) ◽  
Author(s):  
Manal Shawky Hussein ◽  
Rasha Ahmed Gaber ◽  
Hala Mostafa Elsabagh ◽  
Elsayed Mohamed Rageh
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Loss ◽  
Disease Severity ◽  
Nuclear Factor Kappa B ◽  
Severe Disease ◽  
Control Group ◽  
Nuclear Factor ◽  
Larsen Score ◽  
Nuclear Factor Kappa ◽  
Receptor Activator

Abstract Background One of the most important and dangerous complications of rheumatoid arthritis (RA) is bone loss, which manifested by erosions and juxta-articular or systemic bone loss. Anti-carbamylated protein (anti-CarP) antibodies which are also called anti-homocitrulline antibodies have recently been found in RA. Increase anti-CarP antibody titres may lead to severe disease and increase the progression of bone loss. Osteoprotegrin and receptor activator for nuclear factor kappa B and its ligand (RANKL) are the main players in the pathogenesis of osteoporosis. Thus, we aimed to investigate and detect the presence and prevalence of anti-CarP in rheumatoid arthritis and their association with disease severity and osteoporosis, as well as with OPG/RANKL in 80 Egyptian RA patients to highlight this relationship which could be useful in managing RA patients with osteoporosis. Results Serum anti-CarP levels were significantly increased in the RA group compared with the control group (P< 0.001). We found a negative association between anti-CarP and anti-CCP and disease activity (r=−0.878, −0.534, respectively, P<0.001). We also found a positive correlation between anti-CarP and the Larsen score, DEXA score, RF, HAQ, and RANKL (r=0.646, 0.287, 0.243, 0.892, 0.671, 0.869 [respectively], P<0.001) and there was negative correlation between anti-CarP and OPG (r=−0.553, P<0.001). Conclusion Anti-CarP antibodies are associated with disease severity and disability in RA patients. They could play an important and significant role in the pathogenesis of osteoporosis in these patients.

The role of nuclear factor-[kappa ]B in the biology and treatment of multiple myeloma

2001 ◽  
Vol 28 (6) ◽  
pp. 626-633 ◽  
Author(s):  
James R. Berenson ◽  
Hongjin M. Ma ◽  
Robert Vescio
Keyword(s):  
Multiple Myeloma ◽  
Nuclear Factor Kappa B ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa
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