scholarly journals Nitric Oxide Alters the Pattern of Auxin Maxima and PIN-FORMED1 During Shoot Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Inmaculada Sánchez-Vicente ◽  
Tamara Lechón ◽  
María Fernández-Marcos ◽  
Luis Sanz ◽  
Oscar Lorenzo
Keyword(s):  
Nitric Oxide ◽  
Cell Fate ◽  
Stem Elongation ◽  
Shoot Development ◽  
No Production ◽  
Leaf Margin ◽  
Cell Fate Decisions ◽  
Protein Levels ◽  
Auxin Distribution ◽  
Shoot Architecture

Hormone patterns tailor cell fate decisions during plant organ formation. Among them, auxins and cytokinins are critical phytohormones during early development. Nitric oxide (NO) modulates root architecture by the control of auxin spatial patterns. However, NO involvement during the coordination of shoot organogenesis remains unclear. Here, we explore the effect of NO during shoot development by using a phenotypic, cellular, and genetic analysis in Arabidopsis thaliana and get new insights into the characterization of NO-mediated leaf-related phenotypes. NO homeostasis mutants are impaired in several shoot architectural parameters, including phyllotactic patterns, inflorescence stem elongation, silique production, leaf number, and margin. Auxin distribution is a key feature for tissue differentiation and need to be controlled at different levels (i.e., synthesis, transport, and degradation mechanisms). The phenotypes resulting from the introduction of the cue1 mutation in the axr1 auxin resistant and pin1 backgrounds exacerbate the relationship between NO and auxins. Using the auxin reporter DR5:GUS, we observed an increase in auxin maxima under NO-deficient mutant backgrounds and NO scavenging, pointing to NO-ASSOCIATED 1 (NOA1) as the main player related to NO production in this process. Furthermore, polar auxin transport is mainly regulated by PIN-FORMED 1 (PIN1), which controls the flow along leaf margin and venations. Analysis of PIN1 protein levels shows that NO controls its accumulation during leaf development, impacting the auxin mediated mechanism of leaf building. With these findings, we also provide evidence for the NO opposite effects to determine root and shoot architecture, in terms of PIN1 accumulation under NO overproduction.

scholarly journals Generation of cell polarity in plants links endocytosis, auxin distribution and cell fate decisions

Nature ◽  
2008 ◽  
Vol 456 (7224) ◽  
pp. 962-966 ◽  
Author(s):  
Pankaj Dhonukshe ◽  
Hirokazu Tanaka ◽  
Tatsuaki Goh ◽  
Kazuo Ebine ◽  
Ari Pekka Mähönen ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cell Polarity ◽  
Cell Fate Decisions ◽  
Auxin Distribution

scholarly journals Oxygen-dependent ATF-4 stability is mediated by the PHD3 oxygen sensor

Blood ◽  
2007 ◽  
Vol 110 (10) ◽  
pp. 3610-3617 ◽  
Author(s):  
Jens Köditz ◽  
Jutta Nesper ◽  
Marieke Wottawa ◽  
Daniel P. Stiehl ◽  
Gieri Camenisch ◽  
...  
Keyword(s):  
Cell Fate ◽  
Oxygen Sensor ◽  
Hypoxia Inducible Factor ◽  
Adaptive Responses ◽  
Von Hippel Lindau ◽  
Cell Fate Decisions ◽  
Protein Levels ◽  
Activating Transcription Factor 4 ◽  
Domain 3 ◽  
The Unfolded Protein Response

Abstract The activating transcription factor-4 (ATF-4) is translationally induced under anoxic conditions, mediates part of the unfolded protein response following endoplasmic reticulum (ER) stress, and is a critical regulator of cell fate. Here, we identified the zipper II domain of ATF-4 to interact with the oxygen sensor prolyl-4-hydroxylase domain 3 (PHD3). The PHD inhibitors dimethyloxalylglycine (DMOG) and hypoxia, or proteasomal inhibition, all induced ATF-4 protein levels. Hypoxic induction of ATF-4 was due to increased protein stability, but was independent of the ubiquitin ligase von Hippel–Lindau protein (pVHL). A novel oxygen-dependent degradation (ODD) domain was identified adjacent to the zipper II domain. Mutations of 5 prolyl residues within this ODD domain or siRNA-mediated down-regulation of PHD3, but not of PHD2, was sufficient to stabilize ATF-4 under normoxic conditions. These data demonstrate that PHD-dependent oxygen-sensing recruits both the hypoxia-inducible factor (HIF) and ATF-4 systems, and hence not only confers adaptive responses but also cell fate decisions.

Free Arginase-I in Human Pulmonary Microvascular Endothelial Cell Culture Leads to Endothelial Dysfunction and Increased Reactive Oxygen Species.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3041-3041
Author(s):  
John S. Corns ◽  
Leif D Nelin
Keyword(s):  
Nitric Oxide ◽  
Fold Change ◽  
No Production ◽  
Ros Production ◽  
Oxygen Species ◽  
Protein Levels ◽  
Nitrite Production ◽  
Urea Production ◽  
The Media ◽  
Arginase I

Abstract Abstract 3041 Poster Board II-1017 Introduction Endothelial dysfunction in chronic hemolytic diseases (e.g., sickle cell disease) is believed to lead to hemolysis-associated pulmonary hypertension. Dysregulated arginine metabolism, via free arginase-I released during hemolysis, is one mechanism proposed in prior studies. However, the effects of free arginase-I on endothelial cell function have not previously been reported. We hypothesized that free arginase-I would decrease hPMVEC nitric oxide (NO) production and therefore limit NO bioavailability. Methods Cultured human pulmonary microvascular endothelial cells (hPMVEC), at passage 6-8 and approximately 80% confluence, with increasing arginase-I concentrations added to the media (CN: 0 ng prot/mL, A30: 30 ng prot/mL, A90: 90 ng prot/mL) were studied. To maximize arginase-I activity, 0.1 mM MnCl2 (an important cofactor for arginase-I) and 3mM of L-arginine were added to each condition. The hPMVEC were incubated for 24h in normoxia (n=8) or hypoxia (1% O2; n=4), then media was harvested for urea/nitrite analyses and cell protein was harvested for Western blot analyses. ANOVA analyses were conducted to determine statistical significance. Results Urea production significantly increased with increasing media arginase-I in both normoxia (CN: 1.47±0.22, A30: 1.46±0.15, A90: 2.09±0.20 umol/mgPr; p<0.05) and hypoxia (CN: 0.913±0.22, A30: 1.01±0.04, A90: 1.99±0.14 umol/mgPr; p<0.005); interestingly, hypoxia means were significantly lower than those in normoxia (p<0.01). However, the percent change from controls in hypoxia (CN: 100±24, A30: 110±4, A90: 218±15) was significantly higher (p<0.05) than in normoxia conditions (CN: 100±15, A30: 99±10, A90: 142±13). Nitrite production showed no significant change with increasing media arginase-I in normoxia (CN: 17.6±2.4, A30: 20.8±4.6, A90: 18.8±2.1 nmol/mgPr; p=0.79); however, in hypoxia nitrites trended down with increasing media arginase-I (CN: 5.26±0.42, A30: 4.35±0.27, A90: 3.69±0.51 nmol/mgPr; p=0.068). In addition, means for nitrite production in hypoxia were significantly less than in normoxia conditions (p<0.0001). In normoxia, Western blot analyses showed significantly decreased 3-nitrotyrosine (3-NT) levels with increasing media arginase-I (CN: 1.00±0.03, A30: 0.88±0.07, A90: 0.77±0.07 [fold change]; p<0.05). 3-NT expression in hypoxia showed no differences with increasing media arginase-I (CN: 1.90±0.16, A30: 1.88±0.19, A90: 1.75±0.27 [fold change, normalized to normoxia control]; p=0.87); however, hypoxic means were significantly higher than in normoxia conditions (p<0.0001). In normoxia, NAD(P)H oxidase isoform 4 (Nox4) show a decreasing trend in protein levels with increasing media arginase-I (CN: 1.00±0.03, A30: 0.93±0.10, A90: 0.86±0.06 [fold change]), with an increase in Nox4 protein levels in hypoxia with increasing media arginase-I (CN: 1.18±0.02, A30: 1.33±0.08, A90: 1.47±0.01 [fold change, normalized to normoxia control]). The hypoxic levels of Nox4 were also higher than in normoxia conditions. Conclusions As expected, increasing free media arginase-I concentrations in hPMVEC culture resulted in significant increases in urea production in both normoxia and hypoxia. Hypoxia resulted in lower nitrite production by endothelial nitric oxide synthase (eNOS). However, increasing amounts of free arginase-I only affected nitrite production in hypoxia, suggesting that increased arginase-I serum concentrations may also become an important regulator of NO production in clinical cases of hypoxia (e.g., acute chest syndrome and vaso-occlusive crises in sickle cell patients). The concurrent increased expression of 3-NT in hypoxia, despite lower nitrites, implies an increase in reactive oxygen species (ROS). Our preliminary data for Nox4 expression, the predominant source of ROS in endothelial cells, indicates that ROS production via this pathway may increase in hypoxia with increasing free arginase-I. Further studies on how free arginase-I in the media affects endothelial function are warranted, particularly in regards to the mechanism by which free arginase-I leads to greater Nox4 expression and ROS production. We speculate that arginase-I inhibitors may represent a potential therapeutic target in patients with chronic hemolysis and acute hypoxic events. Disclosures No relevant conflicts of interest to declare.

scholarly journals Activity of the β-catenin phosphodestruction complex at cell–cell contacts is enhanced by cadherin-based adhesion

2009 ◽  
Vol 186 (2) ◽  
pp. 219-228 ◽  
Author(s):  
Meghan T. Maher ◽  
Annette S. Flozak ◽  
Adam M. Stocker ◽  
Anjen Chenn ◽  
Cara J. Gottardi
Keyword(s):  
Transcription Factors ◽  
Cell Adhesion ◽  
Cell Fate ◽  
Cell Contacts ◽  
Cell Fate Decisions ◽  
T Cell Factor ◽  
Protein Levels ◽  
Gsk 3Β ◽  
Canonical Wnt ◽  
Cell Cell

It is well established that cadherin protein levels impact canonical Wnt signaling through binding and sequestering β-catenin (β-cat) from T-cell factor family transcription factors. Whether changes in intercellular adhesion can affect β-cat signaling and the mechanism through which this occurs has remained unresolved. We show that axin, APC2, GSK-3β and N-terminally phosphorylated forms of β-cat can localize to cell–cell contacts in a complex that is molecularly distinct from the cadherin–catenin adhesive complex. Nonetheless, cadherins can promote the N-terminal phosphorylation of β-cat, and cell–cell adhesion increases the turnover of cytosolic β-cat. Together, these data suggest that cadherin-based cell–cell adhesion limits Wnt signals by promoting the activity of a junction-localized β-cat phosphodestruction complex, which may be relevant to tissue morphogenesis and cell fate decisions during development.

scholarly journals Retraction Note: Generation of cell polarity in plants links endocytosis, auxin distribution and cell fate decisions

Nature ◽  
2014 ◽  
Vol 511 (7509) ◽  
pp. 370-370 ◽  
Author(s):  
Pankaj Dhonukshe ◽  
Hirokazu Tanaka ◽  
Tatsuaki Goh ◽  
Kazuo Ebine ◽  
Ari Pekka Mähönen ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cell Polarity ◽  
Cell Fate Decisions ◽  
Auxin Distribution

scholarly journals Nitric oxide formation in acutely rejecting cardiac allografts correlates with GTP cyclohydrolase I activity

2005 ◽  
Vol 391 (3) ◽  
pp. 541-547 ◽  
Author(s):  
Galen M. Pieper ◽  
Vani Nilakantan ◽  
Nadine L. N. Halligan ◽  
Ashwani K. Khanna ◽  
Gail Hilton ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Graft Rejection ◽  
Ex Vivo ◽  
No Production ◽  
Gtp Cyclohydrolase I ◽  
Gtp Cyclohydrolase ◽  
Protein Levels ◽  
Acute Graft Rejection ◽  
Cardiac Allografts ◽  
Acute Graft

Inducible nitric oxide synthase (iNOS) is a prominent component of the complex array of mediators in acute graft rejection. While NO production is determined by iNOS expression, BH4 (tetrahydrobiopterin), a cofactor of iNOS synthesized by GTP cyclohydrolase I, has been considered critical in sustaining NO production. In the present study, we examined time-dependent changes in iNOS and GTP cyclohydrolase I in rat cardiac allografts. The increase in iNOS protein and mRNA in allografts was similar at POD4 (post-operative day 4) and POD6. However, the peak increase in intragraft NO level at POD4 was not sustained at POD6. This disparity could not be explained by any decrease in iNOS enzyme activity measured ex vivo with optimal amounts of substrate and cofactors. Lower iNOS activity could be explained by changes in total biopterin levels in allografts at POD4 that was decreased to baseline at POD6. Changes in biopterin production correlated with lower GTP cyclohydrolase I protein levels but not by any change in GTP cyclohydrolase I mRNA. Functionally, allografts displayed bradycardia and distended diastolic and systolic dimensions at POD6 but not at POD4. Likewise, histological rejection scores were increased at POD4 but with a secondary increased stage at POD6. It is hypothesized that the dissimilar amounts of NO at early and later stages of rejection is due to uncoupling of iNOS arising from disproportionate synthesis of BH4. These findings provide insight into a potential pathway regulating NO bioactivity in graft rejection. Such knowledge may potentially assist in the design of newer strategies to prevent acute graft rejection.

scholarly journals High levels of Notch signaling down-regulate Numb and Numblike

2006 ◽  
Vol 175 (4) ◽  
pp. 535-540 ◽  
Author(s):  
Gavin Chapman ◽  
Lining Liu ◽  
Cecilia Sahlgren ◽  
Camilla Dahlqvist ◽  
Urban Lendahl
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Cultured Cells ◽  
Tumor Development ◽  
Proteasome Inhibitor Mg132 ◽  
Cell Fate Decisions ◽  
Protein Levels ◽  
Notch Intracellular Domain ◽  
Low Levels ◽  
Mediated Reduction

Inhibition of Notch signaling by Numb is critical for many cell fate decisions. In this study, we demonstrate a more complex relationship between Notch and the two vertebrate Numb homologues Numb and Numblike. Although Numb and Numblike at low levels of Notch signaling negatively regulated Notch, high levels of Notch signaling conversely led to a reduction of Numb and Numblike protein levels in cultured cells and in the developing chick central nervous system. The Notch intracellular domain but not the canonical Notch downstream proteins Hes 1 and Hey 1 caused a reduction of Numb and Numblike. The Notch-mediated reduction of Numblike required the PEST domain in the Numblike protein and was blocked by the proteasome inhibitor MG132. Collectively, these observations reveal a reciprocal negative regulation between Notch and Numb/Numblike, which may be of relevance for stabilizing asymmetric cell fate switches and for tumor development.

Steroid hormones augment nitric oxide synthase activity and expression in rat uterus

2003 ◽  
Vol 15 (5) ◽  
pp. 269 ◽  
Author(s):  
D. Ogando ◽  
M. Farina ◽  
M. L. Ribeiro ◽  
S. Perez Martinez ◽  
M. Cella ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ovariectomized Rats ◽  
Ovariectomized Rat ◽  
No Production ◽  
Rat Uterus ◽  
Western Blots ◽  
Protein Levels ◽  
Inos Inhibitor ◽  
Oxide Synthase ◽  
Expression And Activity

Nitric oxide (NO) is synthesized in a variety of tissues, including rat uterus, from L-arginine by NO synthase (NOS), of which there are three isoforms, namely neuronal, endothelial and inducible NOS (nNOS, eNOS and iNOS, respectively). Nitric oxide is an important regulator of the biology and physiology of the organs of the reproductive system, including the uterus. Some studies have shown increased variation in NO production and NOS expression during the oestrous cycle. However, the factors that regulate NO production in the uterus remain unclear. Therefore, in the present study, we investigated the effect of sex steroids on NOS expression and activity in the ovariectomized rat uterus. Ovariectomized rats received progesterone (4 mg per rat) or 17β-oestradiol (1 μg per rat). All rats were killed 18 h after treatment. Both progesterone and oestradiol were able to augment NOS activity. The effect of oestradiol was abolished by pre-incubation with 500 μM aminoguanidine, an iNOS inhibitor, or by coadministration of oestradiol with 3 mg kg−1 dexamethasone, but the effect of progesterone was not affected by these treatments. Uterine nNOS, eNOS and iNOS protein levels were assessed using Western blots. Ovariectomized rat uteri expressed iNOS and eNOS. Progesterone increased the expression of eNOS and iNOS, whereas oestradiol increased iNOS expression only. These results suggest that oestradiol and progesterone are involved in the regulation of NOS expression and activity during pregnancy and implantation in the rat.

scholarly journals miR-129-5p Regulates the Immunomodulatory Functions of Adipose-Derived Stem Cells via Targeting Stat1 Signaling

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
He-Yang Zhang ◽  
Yu-Han Wang ◽  
Yan Wang ◽  
Yan-Nv Qu ◽  
Xiao-Hui Huang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Stem Cells ◽  
Inflammatory Factors ◽  
Inos Mrna ◽  
No Production ◽  
Adipose Derived Stem Cells ◽  
Protein Levels ◽  
Bowel Diseases

Adipose-derived stem cells (ASCs) have become one of the most promising stem cell populations for cell-based therapies in regenerative medicine and for autoimmune disorders owing to their multilineage differentiation and immunomodulatory capacities, respectively. One advantage of ASC-based therapy lies in their immunosuppressive potential. However, how to get ASCs to provide consistent immunosuppression remains unclear. In the current study, we found that miR-129-5p was induced in ASCs treated with inflammatory factors. ASCs with miR-129-5p knockdown exhibited enhanced immunosuppressive capacity, as evidenced by reduced expression of proinflammatory factors, with concurrent increased expression of inducible nitric oxide synthases (iNOS) and nitric oxide (NO) production. These cells also had an increased capacity to inhibit T cell proliferation in vitro. ASCs with miR-129-5p knockdown alleviated inflammatory bowel diseases and promoted tumor growth in vivo. Consistently, ASCs that overexpressed miR-129-5p exhibited reduced iNOS expression. Furthermore, we show that miR-129-5p knockdown in ASCs results in hyperphosphorylation of signal transducer and activator of transcription 1 (Stat1). When fludarabine, an inhibitor of Stat1 activation, was added to ASCs with miR-129-5p knockdown, iNOS mRNA and protein levels were significantly reduced. Collectively, these results reveal a new role for miR-129-5p in regulating the immunomodulatory activities of ASCs by targeting Stat1 activation. These novel insights into the mechanisms of ASC immunoregulation may lead to the consistent production of ASCs with strong immunosuppressive functions and thus better clinical utility of these cells.

scholarly journals Enhanced Immune Response by Vacuoles isolated from Saccharomyces cerevisiae in RAW 264.7 Macrophages

2021 ◽  
Author(s):  
Su-Min Lee ◽  
Wooil Choi ◽  
Woo-Ri Shin ◽  
Yang-Hoon Kim ◽  
Jiho Min
Keyword(s):  
Nitric Oxide ◽  
Immune Response ◽  
Inflammatory Cytokines ◽  
Membrane Vesicles ◽  
No Production ◽  
Macrophage Activity ◽  
Protein Levels ◽  
Immune Mediated ◽  
Factor Α ◽  
Pro Inflammatory Cytokines

Vacuoles are membrane vesicles in eukaryotic cells, the digestive system of cells that break down substances absorbed outside the cell and digest the useless components of the cell itself. Researches on anti-cancer and intractable diseases using vacuoles are being actively conducted. The practical application of this study to animals requires the determination of the biocompatibility of vacuole. In the present study, we evaluated the effects of vacuoles isolated from S. cerevisiae in RAW264.7 cells. This showed a significant increase in the production of nitric oxide produced by macrophage activity. Using Reactive Oxygen Species (ROS) Assay, we identified that ROS is increased in a manner dependent on vacuole concentration. Western blot analysis showed that vacuole concentration-dependently increased protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2). Therefore, iNOS expression was stimulated to induce Nitric oxide (NO) production. In addition, pro-inflammatory cytokines levels promoted, such as interleukin 6 and tumor necrosis factor -α. In summary, vacuoles activate the immune response of macrophages by promoting the production of immune-mediated transporters NO, ROS, and pro-inflammatory cytokines.

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