scholarly journals Nicotinamide Mononucleotide Supplementation

2021 ◽  
Author(s):  
Tamás Kiss
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Molecular Mechanisms ◽  
Bioinformatic Analysis ◽  
Vascular Cognitive Impairment ◽  
Vascular Aging ◽  
Nad Metabolism ◽  
Nicotinamide Mononucleotide

Vascular cognitive impairment (VCI) is a major cause of dementia among elderly individuals. Understanding molecular mechanisms behind vascular aging is essential to develop novel interventional strategies for the treatment and prevention of VCI. Recent studies have provided critical evidence that vascular aging is characterized by cellular NAD+ depletion. In our studies we systematically investigated the effects of boosting cellular NAD+ levels by the use of nicotinamide mononucleotide (NMN), an intermediate of NAD+ metabolism. First, we conducted in vitro examination of cultured cerebromicrovascular endothelial cells (CMVES) isolated from young and aged F344xBN rats. We have shown that NMN treatment attenuates oxidative stress and rescues angiogenic capacity in aged CMVES. Next, in vivo aged C57BL/6 mice were treated daily with NMN for 14 days. NMN treatment rescued cognitive performance, motor function and neurovascular coupling in aged animals. To understand the fundamental gene regulation underlying the beneficial effects of NMN treatment, we generated a miRNA profile from the aorta and a gene expression profile from isolated brain endothelial cells. Bioinformatic analysis revealed that the effects of NMN treatment were mediated by the sirtuin pathway and induced gene expression changes associated with mitochondrial rejuvenation, anti-inflammatory and anti- apoptotic pathways.

scholarly journals Elevated expression of NEU1 sialidase in idiopathic pulmonary fibrosis provokes pulmonary collagen deposition, lymphocytosis, and fibrosis

2016 ◽  
Vol 310 (10) ◽  
pp. L940-L954 ◽  
Author(s):  
Irina G. Luzina ◽  
Virginia Lockatell ◽  
Sang W. Hyun ◽  
Pavel Kopach ◽  
Phillip H. Kang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Recombinant Adenovirus ◽  
Global Gene Expression

Idiopathic pulmonary fibrosis (IPF) poses challenges to understanding its underlying cellular and molecular mechanisms and the development of better therapies. Previous studies suggest a pathophysiological role for neuraminidase 1 (NEU1), an enzyme that removes terminal sialic acid from glycoproteins. We observed increased NEU1 expression in epithelial and endothelial cells, as well as fibroblasts, in the lungs of patients with IPF compared with healthy control lungs. Recombinant adenovirus-mediated gene delivery of NEU1 to cultured primary human cells elicited profound changes in cellular phenotypes. Small airway epithelial cell migration was impaired in wounding assays, whereas, in pulmonary microvascular endothelial cells, NEU1 overexpression strongly impacted global gene expression, increased T cell adhesion to endothelial monolayers, and disrupted endothelial capillary-like tube formation. NEU1 overexpression in fibroblasts provoked increased levels of collagen types I and III, substantial changes in global gene expression, and accelerated degradation of matrix metalloproteinase-14. Intratracheal instillation of NEU1 encoding, but not control adenovirus, induced lymphocyte accumulation in bronchoalveolar lavage samples and lung tissues and elevations of pulmonary transforming growth factor-β and collagen. The lymphocytes were predominantly T cells, with CD8+ cells exceeding CD4+ cells by nearly twofold. These combined data indicate that elevated NEU1 expression alters functional activities of distinct lung cell types in vitro and recapitulates lymphocytic infiltration and collagen accumulation in vivo, consistent with mechanisms implicated in lung fibrosis.

Serial analysis of gene expression (SAGE) during porcine embryo development

2004 ◽  
Vol 16 (2) ◽  
pp. 87 ◽  
Author(s):  
Le Ann Blomberg ◽  
Kurt A. Zuelke
Keyword(s):  
Gene Expression ◽  
Functional Genomics ◽  
Embryo Development ◽  
Molecular Mechanisms ◽  
Physiological Role ◽  
Transgenic Animals ◽  
Specific Gene ◽  
Research Strategies

Functional genomics provides a powerful means for delving into the molecular mechanisms involved in pre-implantation development of porcine embryos. High rates of embryonic mortality (30%), following either natural mating or artificial insemination, emphasise the need to improve the efficiency of reproduction in the pig. The poor success rate of live offspring from in vitro-manipulated pig embryos also hampers efforts to generate transgenic animals for biotechnology applications. Previous analysis of differential gene expression has demonstrated stage-specific gene expression for in vivo-derived embryos and altered gene expression for in vitro-derived embryos. However, the methods used to date examine relatively few genes simultaneously and, thus, provide an incomplete glimpse of the physiological role of these genes during embryogenesis. The present review will focus on two aspects of applying functional genomics research strategies for analysing the expression of genes during elongation of pig embryos between gestational day (D) 11 and D12. First, we compare and contrast current methodologies that are being used for gene discovery and expression analysis during pig embryo development. Second, we establish a paradigm for applying serial analysis of gene expression as a functional genomics tool to obtain preliminary information essential for discovering the physiological mechanisms by which distinct embryonic phenotypes are derived.

Abstract 116: Arterial Endothelial Cell Has Stronger Angiogenic Potential Compared To Venous Endothelial Cell Through Up-regulation Of Endogenous FGF2 And FGF5 Expression In 3D Microfluidic System

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Ha-Rim Seo ◽  
Hyo Eun Jeong ◽  
Hyung Joon Joo ◽  
Seung-Cheol Choi ◽  
Jong-Ho Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Assay System ◽  
Vascular Density ◽  
Angiogenic Potential ◽  
Angiogenesis Assay

Background: Human body contains many kinds of different type of endothelial cells (EC). However, cellular difference of their angiogenic potential has been hardly understood. We compared in vitro angiogenic potential between arterial EC and venous EC and investigated its underlying molecular mechanisms. Method: Used human aortic endothelial cells (HAEC) which was indicated from arterial EC and human umbilical vein endothelial cells (HUVEC) indicated from venous EC. To explore angiogenic potential in detail, we adopted a novel 3D microfluidic angiogenesis assay system, which closely mimic in vivo angiogenesis. Results: In 3D microfluidic angiogenesis assay system, HAEC demonstrated stronger angiogenic potential compared to HUVEC. HAEC maintained its profound angiogenic property under different biophysical conditions. In mRNA microarray sorted on up- regulated or down-regulated genes, HAEC demonstrated significantly higher expression of gastrulation brain homeobox 2 (GBX2), fibroblast grow factor 2 (FGF2), FGF5 and collagen 8a1. Angiogenesis-related protein assay revealed that HAEC has higher secretion of endogenous FGF2 than HUVEC. HAEC has only up-regulated FGF2 and FGF5 in this part of FGF family. Furthermore, FGF5 expression under vascular endothelial growth factor-A (VEGF-A) stimulation was higher in HAEC compared to HUVEC although VEGF-A augmented FGF5 expression in both HAEC and HUVEC. Those data suggested that FGF5 expression in both HAEC and HUVEC is partially dependent to VEGF-A stimulate. HUVEC and HAEC reduced vascular density after FGF2 and FGF5 siRNA treat. Conclusion: HAEC has stronger angiogenic potential than HUVEC through up-regulation of endogenous FGF2 and FGF5 expression

Kaposi sarcoma-associated herpesvirus (KSHV) induces heme oxygenase-1 expression and activity in KSHV-infected endothelial cells

Blood ◽  
2004 ◽  
Vol 103 (9) ◽  
pp. 3465-3473 ◽  
Author(s):  
Shane C. McAllister ◽  
Scott G. Hansen ◽  
Rebecca A. Ruhl ◽  
Camilo M. Raggo ◽  
Victor R. DeFilippis ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Heme Oxygenase ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Kaposi Sarcoma ◽  
Heme Oxygenase 1 ◽  
Spindle Cell Proliferation

Abstract Kaposi sarcoma (KS) is the most common AIDS-associated malignancy and is characterized by angiogenesis and the presence of spindle cells. Kaposi sarcoma-associated herpesvirus (KSHV) is consistently associated with all clinical forms of KS, and in vitro infection of dermal microvascular endothelial cells (DMVECs) with KSHV recapitulates many of the features of KS, including transformation, spindle cell proliferation, and angiogenesis. To study the molecular mechanisms of KSHV pathogenesis, we compared the protein expression profiles of KSHV-infected and uninfected DMVECs. This comparison revealed that heme oxygenase-1 (HO-1), the inducible enzyme responsible for the rate-limiting step in heme catabolism, was up-regulated in infected endothelial cells. Recent evidence suggests that the products of heme catabolism have important roles in endothelial cell biology, including apoptosis and angiogenesis. Here we show that HO-1 mRNA and protein are up-regulated in KSHV-infected cultures. Comparison of oral and cutaneous AIDS-KS tissues with normal tissues revealed that HO-1 mRNA and protein were also up-regulated in vivo. Increased HO-1 enzymatic activity in vitro enhanced proliferation of KSHV-infected DMVECs in the presence of free heme. Treatment with the HO-1 inhibitor chromium mesoporphyrin IX abolished heme-induced proliferation. These data suggest that HO-1 is a potential therapeutic target for KS that warrants further study. (Blood. 2004;103: 3465-3473)

scholarly journals DEPTOR Deficiency-Mediated mTORc1 Hyperactivation in Vascular Endothelial Cells Promotes Angiogenesis

2018 ◽  
Vol 46 (2) ◽  
pp. 520-531 ◽  
Author(s):  
Yan Ding ◽  
Lanlan Shan ◽  
Wenqing Nai ◽  
Xiaojun Lin ◽  
Ling Zhou ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Gene Knockout ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Tube Formation ◽  
Vascular Endothelial

Background/Aims: The mechanistic target of rapamycin (mTOR) signaling pathway is essential for angiogenesis and embryonic development. DEP domain-containing mTOR-interacting protein (DEPTOR) is an mTOR binding protein that functions to inhibit the mTOR pathway In vitro experiments suggest that DEPTOR is crucial for vascular endothelial cell (EC) activation and angiogenic responses. However, knowledge of the effects of DEPTOR on angiogenesis in vivo is limited. This study aimed to determine the role of DEPTOR in tissue angiogenesis and to elucidate the molecular mechanisms. Methods: Cre/loxP conditional gene knockout strategy was used to delete the Deptor gene in mouse vascular ECs. The expression or distribution of cluster of differentiation 31 (CD31), vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1 alpha (HIF-1α) were detected by immunohistochemical staining or western blot. Tube formation assay was used to measure angiogenesis in vitro. Results: Deptor knockdown led to increased expression of CD31, VEGF and HIF-1α in heart, liver, kidney and aorta. After treatment with rapamycin, their expression was significantly down regulated. In vitro, human umbilical vein endothelial cells (HUVECs) were transfected with DEPTOR-specific small interfering RNA (siRNA), which resulted in a significant increase in endothelial tube formation and migration rates. In contrast, DEPTOR overexpression markedly reduced the expression of CD31, VEGF and HIF-1α. Conclusions: Our findings demonstrated that deletion of the Deptor gene in vascular ECs resulted in upregulated expression of CD31 and HIF-1α, and further stimulated the expression of VEGF which promoted angiogenesis, indicating that disruption of normal angiogenic pathways may occur through hyperactivation of the mTORC1/HIF-1α/VEGF signaling pathway.

Bidirectional Oscillatory Shear Stress Increases Pro-Atherogenic Gene Expressions (I-CAM1, E-Selectin and IL-6) in Endothelial Cells

2011 ◽  
Author(s):  
Amlan Chakraborty ◽  
Venkatakrishna R. Jala ◽  
Sutirtha Chakraborty ◽  
R. Eric Berson ◽  
M. Keith Sharp ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Atherosclerotic Plaque ◽  
Inflammatory Diseases ◽  
Leukotriene B4 ◽  
Oscillatory Shear ◽  
Gene Expressions

Wall shear stress (WSS) plays a key role in altering intracellular pathways and gene expression of endothelial cells, and has significant impacts on atherosclerotic plaque development (1–3). Further, the atherogenic regulators Leukotriene B4 (LTB4) and Lipopolysaccharide (LPS) have significant impacts on the pathophysiology of many inflammatory diseases. This study investigates the effects of oscillatory shear directionality on pro-atherogenic gene expression (I-CAM, E-Selectin, and IL-6) in the presence of LTB4 and LPS. An orbital shaker was used to expose the endothelial cells to oscillatory shear in culture dishes, and Computational fluid dynamics (CFD) was applied to quantify the shear stress on the bottom of the orbiting dish. Directionality of oscillatory shear was characterized by a newly developed hemodynamic parameter — Directional oscillatory shear index (DOSI), which was demonstrated in a previous study to significantly impact cell morphology (4). Results showed that DOSI significantly altered gene expression. Therefore, directionality of shear modulates atherosclerotic gene expression in vitro and thus, may influence the formation of atherosclerotic plaque in vivo.

scholarly journals Candida albicans RIM101 pH Response Pathway Is Required for Host-Pathogen Interactions

2000 ◽  
Vol 68 (10) ◽  
pp. 5953-5959 ◽  
Author(s):  
Dana Davis ◽  
John E. Edwards ◽  
Aaron P. Mitchell ◽  
Ashraf S. Ibrahim
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Candida Albicans ◽  
Marked Reduction ◽  
Endothelial Damage ◽  
Systemic Candidiasis ◽  
Ph Response

ABSTRACT The ability of Candida albicans to respond to diverse environments is critical for its success as a pathogen. TheRIM101 pathway controls gene expression and the yeast-to-hyphal transition in C. albicans in response to changes in environmental pH in vitro. In this study, we found that theRIM101 pathway is necessary in vivo for pathogenesis. First, we show thatrim101−/rim101− andrim8−/rim8− mutants have a significant reduction in virulence using the mouse model of hematogenously disseminated systemic candidiasis. Second, these mutants show a marked reduction in kidney pathology. Third, therim101−/rim101− andrim8−/rim8− mutants show defects in the ability to damage endothelial cells in situ. Finally, we show that an activated allele of RIM101, RIM101-405, is a suppressor of the rim8− mutation in vivo as it rescues the virulence, histological, and endothelial damage defects of the rim8−/rim8− mutant. These results demonstrate that the RIM101 pathway is required for C. albicans virulence in vivo and that the function of Rim8p in pathogenesis is to activate Rim101p.

scholarly journals FAM64A Promotes Prostate Cancer Growth In Vivo and In Vitro

2020 ◽  
Author(s):  
Feilun Cui ◽  
Zhipeng Xu ◽  
Yumei Lv ◽  
Jianpeng Hu
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Bioinformatic Analysis ◽  
In Vitro Assays ◽  
Multiple Cancer ◽  
Cell Matrix ◽  
Public Datasets

Abstract Background Prostate cancer (PCa) is the most common type of human cancer in males. However, the mechanisms underlying PCa tumorigenesis remained unclear.Methods The present study evaluated the expression levels of FAM64A in PCa by using 5 public datasets, including GSE8511, GSE45016, GSE55945, GSE38241 and GSE17951. Then, in vivo and in vitro assays were conducted to detect the biological functions of FAM64A in PCa. Microarray and bioinformatic analysis were carried out to detect the downstream targets and pathways regulated by FAM64A.Results In this study, we for first time demonstrate FAM64A as a biomarker for PCa. FAM64A was found to be overexpressed in PCa compared to normal samples. Higher FAM64A expression were found in Gleason score (GS) ≥ 8 PCa compared to GS < 8 PCa samples, in N1 staging compared to N1 staging PCa samples, and T3/4 staging compared to T1 staging PCa. Moreover, higher FAM64A expression was correlated to shorter survival time in PCa. Knockdown of FAM64A significantly suppressed PCa cell proliferation and colony formation, however, induced PCa apoptosis in vivo and in vitro. Bioinformatics analysis combined with microarray analysis revealed FAM64A played crucial roles in regulating multiple cancer related pathways, including cell-matrix adhesion and cAMP signaling pathway. Conclusions These results showed FAM64A could serve as a novel biomarker for PCa and will be helpful to understand the underlying FAM64A -related molecular mechanisms in the progression of PCa.

scholarly journals Retinoic acid activates interferon regulatory factor-1 gene expression in myeloid cells

Blood ◽  
1996 ◽  
Vol 88 (1) ◽  
pp. 114-123 ◽  
Author(s):  
S Matikainen ◽  
T Ronni ◽  
M Hurme ◽  
R Pine ◽  
I Julkunen
Keyword(s):  
Gene Expression ◽  
Retinoic Acid ◽  
Growth Inhibition ◽  
Molecular Mechanisms ◽  
Gene Activation ◽  
Oligoadenylate Synthetase ◽  
Nb4 Cells ◽  
Drug Of Choice

All-trans-retinoic acid (ATRA) is the drug of choice in the treatment of acute promyelocytic leukemia (APL). ATRA induces both in vitro and in vivo differentiation of APL cells into mature granulocytes. However, the molecular mechanisms involved in ATRA-dependent growth inhibition and cellular differentiation are not presently understood. The NB4 cell line, which is derived from the bone marrow of a patient with APL during relapse, can be used as a model system to study the growth and differentiation of APL cells. Because interferon (IFN) regulatory factors (IRF-1 and IRF-2) and other IFN-inducible gene products regulate cell growth, we analyzed the effects of ATRA on the expression of these genes. We show that ATRA directly activates IRF-1 gene expression, followed by activation of IRF-2 and 2′–5′ oligoadenylate synthetase (OAS) gene expression with slower kinetics. In addition to NB4 cells, ATRA also activated IRF-1 gene expression in HL-60, U937, and THP-1 cells, which all respond to ATRA by growth inhibition. A more than additive increase in IRF-1 gene expression was seen with ATRA and IFN-gamma in NB4 cells. ATRA did not activate nuclear factor kappa B or signal transducer and activator of transcription (STAT) activation pathways, suggesting that an alternate mechanism is involved in IRF-1 gene activation. The ATRA-induced expression of IRF-1, an activator of transcription and repressor of transformation, may be one of the molecular mechanisms of ATRA-induced growth inhibition, and the basis for the synergistic actions of ATRA and IFNs in myeloid leukemia cells.

scholarly journals LINC00467 Promotes Tumor Progression via Regulation of the NF-kb Signal Axis in Bladder Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiawei Xiao ◽  
Lian Gong ◽  
Mengqing Xiao ◽  
Dong He ◽  
Liang Xiang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Animal Experiments ◽  
Bioinformatic Analysis ◽  
New Strategy ◽  
Patient Prognosis

PurposeLong non-coding RNAs (lncRNAs) play an important role in the occurrence and development of bladder cancer, but the underlying molecular mechanisms remain largely unknown. In this study, we found that LINC00467 was significantly highly expressed in bladder cancer through bioinformatic analysis. The present study aimed to explore the role of LINC00467 in bladder cancer and its possible underlying molecular mechanisms.MethodsThe expression of LINC00467 was obtained from GEO (GSE31189), the TCGA database, and qRT-PCR. The role of LINC00467 in bladder cancer was assessed both in vitro and in vivo. RIP, RNA pulldown, and CO-IP were used to demonstrate the potential mechanism by which LINC00467 regulates the progression of bladder cancer.ResultsThrough the analysis of GEO (GSE133624) and the TCGA database, it was found that LINC00467 was highly expressed in bladder cancer tissues and that the expression of LINC00467 was significantly negatively correlated with patient prognosis. Cell and animal experiments suggest that LINC00467 promotes the proliferation and invasion of bladder cancer cells. On the one hand, LINC00467 can directly bind to NF-kb-p65 mRNA to stabilize its expression. On the other hand, LINC00467 can directly bind to NF-kb-p65 to promote its translocation into the nucleus to activate the NF-κB signaling pathway, which promotes the progression of bladder cancer.ConclusionsLINC00467 is highly expressed in bladder cancer and can promote the progression of bladder cancer by regulating the NF-κB signaling pathway. Therefore, targeting LINC00467 is very likely to provide a new strategy for the treatment of bladder cancer and for improving patient prognosis.

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