scholarly journals A steroid hormone regulates growth in response to oxygen availability

2021 ◽  
Author(s):  
Goerge Kapali ◽  
Viviane Callier ◽  
Hailey Broeker ◽  
Parth Tank ◽  
Samuel Gascoigne ◽  
...  
Keyword(s):  
Body Size ◽  
Steroid Hormone ◽  
Insulin Binding ◽  
Growth Suppression ◽  
Low Oxygen ◽  
Physiological Mechanisms ◽  
Hypoxic Conditions ◽  
Drosophila Larvae ◽  
Negative Effect ◽  
Almost All

In almost all animals, physiologically low oxygen (hypoxia) during development slows growth and reduces adult body size. The developmental mechanisms that determine growth under hypoxic conditions are, however, poorly understood. One hypothesis is that the effect of hypoxia on growth and final body size is a non-adaptive consequence of the cell-autonomous effects of hypoxia on cellular metabolism. Alternatively, the effect may be an adaptive coordinated response mediated through systemic physiological mechanisms. Here we show that the growth and body size response to moderate hypoxia (10% O2) in Drosophila melanogaster is systemically regulated via the steroid hormone ecdysone, acting partially through the insulin-binding protein Imp-L2. Ecdysone is necessary to reduce growth in response to hypoxia: hypoxic growth suppression is ameliorated when ecdysone synthesis is inhibited. This hypoxia-suppression of growth is mediated by the insulin/IGF-signaling (IIS) pathway. Hypoxia reduces systemic IIS activity and the hypoxic growth-response is eliminated in larvae with suppressed IIS. Further, loss of Imp-L2, an ecdysone-response gene that suppresses systemic IIS, significantly reduces the negative effect of hypoxia on final body size. Collectively, these data indicate that growth suppression in hypoxic Drosophila larvae is accomplished by systemic endocrine mechanisms rather than direct suppression of tissue aerobic metabolism.

scholarly journals Connectivity Map Analysis Indicates PI3K/Akt/mTOR Inhibitors as Potential Anti-Hypoxia Drugs in Neuroblastoma

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2809
Author(s):  
Paolo Uva ◽  
Maria Carla Bosco ◽  
Alessandra Eva ◽  
Massimo Conte ◽  
Alberto Garaventa ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Drug Repurposing ◽  
Enrichment Analysis ◽  
Mtor Inhibitors ◽  
Gene Set Enrichment Analysis ◽  
Low Oxygen ◽  
Connectivity Map ◽  
Hypoxic Conditions ◽  
Connectivity Score

Neuroblastoma (NB) is one of the deadliest pediatric cancers, accounting for 15% of deaths in childhood. Hypoxia is a condition of low oxygen tension occurring in solid tumors and has an unfavorable prognostic factor for NB. In the present study, we aimed to identify novel promising drugs for NB treatment. Connectivity Map (CMap), an online resource for drug repurposing, was used to identify connections between hypoxia-modulated genes in NB tumors and compounds. Two sets of 34 and 21 genes up- and down-regulated between hypoxic and normoxic primary NB tumors, respectively, were analyzed with CMap. The analysis reported a significant negative connectivity score across nine cell lines for 19 compounds mainly belonging to the class of PI3K/Akt/mTOR inhibitors. The gene expression profiles of NB cells cultured under hypoxic conditions and treated with the mTORC complex inhibitor PP242, referred to as the Mohlin dataset, was used to validate the CMap findings. A heat map representation of hypoxia-modulated genes in the Mohlin dataset and the gene set enrichment analysis (GSEA) showed an opposite regulation of these genes in the set of NB cells treated with the mTORC inhibitor PP242. In conclusion, our analysis identified inhibitors of the PI3K/Akt/mTOR signaling pathway as novel candidate compounds to treat NB patients with hypoxic tumors and a poor prognosis.

scholarly journals Hypoxia-Induced Gene Expression Occurs Solely through the Action of Hypoxia-Inducible Factor 1α (HIF-1α): Role of Cytoplasmic Trapping of HIF-2α

2003 ◽  
Vol 23 (14) ◽  
pp. 4959-4971 ◽  
Author(s):  
Sang-ki Park ◽  
Agnes M. Dadak ◽  
Volker H. Haase ◽  
Lucrezia Fontana ◽  
Amato J. Giaccia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Activity ◽  
Hypoxia Inducible Factor ◽  
Low Oxygen ◽  
Hypoxic Conditions ◽  
Show Evidence ◽  
Dependent Protein ◽  
A Cell ◽  
Cell Type Specific ◽  
Inducible Genes

ABSTRACT The hypoxia-inducible factors 1α (HIF-1α) and 2α (HIF-2α) have extensive structural homology and have been identified as key transcription factors responsible for gene expression in response to hypoxia. They play critical roles not only in normal development, but also in tumor progression. Here we report on the differential regulation of protein expression and transcriptional activity of HIF-1α and -2α by hypoxia in immortalized mouse embryo fibroblasts (MEFs). We show that oxygen-dependent protein degradation is restricted to HIF-1α, as HIF-2α protein is detected in MEFs regardless of oxygenation and is localized primarily to the cytoplasm. Endogenous HIF-2α remained transcriptionally inactive under hypoxic conditions; however, ectopically overexpressed HIF-2α translocated into the nucleus and could stimulate expression of hypoxia-inducible genes. We show that the factor inhibiting HIF-1 can selectively inhibit the transcriptional activity of HIF-1α but has no effect on HIF-2α-mediated transcription in MEFs. We propose that HIF-2α is not a redundant transcription factor of HIF-1α for hypoxia-induced gene expression and show evidence that there is a cell type-specific modulator(s) that enables selective activation of HIF-1α but not HIF-2α in response to low-oxygen stress.

Microstructure and Abrasion Resistance of WC-Co Coatings Produced by High Velocity Oxy-Fuel Spraying

1997 ◽  
Author(s):  
M.S.A. Khan ◽  
T.W. Clyne ◽  
A.J. Sturgeon
Keyword(s):  
Wear Resistance ◽  
High Velocity ◽  
Abrasion Resistance ◽  
Close Correlation ◽  
Low Oxygen ◽  
Hvof Spraying ◽  
Degree Of Reaction ◽  
Small Rise ◽  
Negative Effect ◽  
Positive Effect

Abstract Coatings have been produced by HVOF spraying of four different WC-Co powders, using two fuel gases and two oxygen contents in the flame, and characterised in terms of microstructure and resistance to abrasive wear. It is concluded that there is a close correlation between high levels of chemical reaction, occurring during spraying (and possibly during powder production), and poor wear resistance. Good wear resistance is favoured by using low porosity powders, which interact with the atmosphere less readily during spraying, and also by using a flame with a relatively low oxygen content. This probably minimises the degree of reaction by ensuring that conditions are reducing. Use of propylene rather than hydrogen gives coatings with slightly better wear resistance, despite the fact that the flame temperatures are higher. It is concluded that, for this relatively small rise in temperature, the positive effect on inter-splat cohesion seems to outweigh the negative effect of increased decarburisation.

scholarly journals Effect of Thidiazuron on Terpene Volatile Constituents and Terpenoid Biosynthesis Pathway Gene Expression of Shine Muscat (Vitis labrusca × V. vinifera) Grape Berries

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2578
Author(s):  
Wu Wang ◽  
Muhammad Khalil-Ur-Rehman ◽  
Ling-Ling Wei ◽  
Niels J. Nieuwenhuizen ◽  
Huan Zheng ◽  
...  
Keyword(s):  
Volatile Compounds ◽  
Sensory Characteristics ◽  
The Novel ◽  
Terpene Biosynthesis ◽  
Grape Berries ◽  
Fruit Drop ◽  
Pathway Gene ◽  
Negative Effect ◽  
Key Genes ◽  
Almost All

Volatile compounds are considered to be essential for the flavor and aroma quality of grapes. Thidiazuron (TDZ) is a commonly used growth regulator in grape cultivation that stimulates larger berries and prevents fruit drop. This study was conducted to investigate the effect of TDZ on the production of aroma volatiles and to identify the key genes involved in the terpene biosynthesis pathways that are affected by this compound. Treatment with TDZ had a negative effect on the concentration of volatile compounds, especially on monoterpenes, which likely impacts the sensory characteristics of the fruit. The expression analysis of genes related to the monoterpenoid biosynthesis pathways confirmed that treatment with TDZ negatively regulated the key genes DXS1, DXS3, DXR, HDR, VvPNGer and VvPNlinNer1. Specifically, the expression levels of the aforementioned genes were down-regulated in almost all berry development stages in the TDZ-treated samples. The novel results from the present study can be used to aid in the development of food products which maintain the flavor quality and sensory characteristics of grape. Furthermore, these findings can provide the theoretical basis that can help to optimize the utilization of TDZ for the field production of grapes at a commercial scale.

scholarly journals Responses of food web to hypolimnetic aeration in Lake Vesijärvi

Hydrobiologia ◽  
2020 ◽  
Vol 847 (21) ◽  
pp. 4503-4523 ◽  
Author(s):  
Jukka Ruuhijärvi ◽  
Tommi Malinen ◽  
Kirsi Kuoppamäki ◽  
Pasi Ala-Opas ◽  
Mika Vinni
Keyword(s):  
Body Size ◽  
Food Web ◽  
Harmful Algal Blooms ◽  
Algal Blooms ◽  
Perca Fluviatilis ◽  
Fish Predation ◽  
Filamentous Cyanobacteria ◽  
Low Oxygen ◽  
High Quality ◽  
Oxygen Conditions

AbstractWe studied the responses of a food web, especially fish and zooplankton, to summertime aeration, pumping of oxygen-rich epilimnetic water to the hypolimnion in Lake Vesijärvi, southern Finland. The aim of hypolimnetic aeration was to reduce internal loading of phosphorus from sediment. The population of smelt (Osmerus eperlanus L.), the main planktivore of the pelagial area, collapsed during the two 1st years of aeration due to increased temperature and low oxygen concentrations in the hypolimnion. The population recovered after the 4th year of hypolimnetic aeration, when oxygen conditions were improved. Despite elevated hypolimnetic temperature, smelt reached exceptionally high abundance, which led to a significant reduction in cladoceran body size. The density of perch (Perca fluviatilis L.) increased at first, but then decreased when the proportion of smelt and cyprinids increased. Biomasses of Daphnia decreased probably as a result of the disappearance of dark, low-oxygen deep-water refuge against fish predation and low availability of nutritionally high-quality algae. Occasionally filamentous cyanobacteria, such as turbulence tolerant Planktothrix agardhii (Gomont), were abundant, suggesting deteriorated food resources for zooplankton. The responses of food web were controversial with respect to the aim of the management, which was to prevent the occurrence of harmful algal blooms.

Jasus lalandii 'walkouts' or mass strandings in South Africa during the 1990s: an overview

2001 ◽  
Vol 52 (8) ◽  
pp. 1085 ◽  
Author(s):  
Andrew C. Cockcroft
Keyword(s):  
South Africa ◽  
West Coast ◽  
The Other ◽  
Fishing Industry ◽  
Low Oxygen ◽  
Rock Lobster ◽  
The West ◽  
Hypoxic Conditions ◽  
Oxygen Conditions ◽  
Mass Mortalities

Faunal mass mortalities are a sporadic, but not uncommon, feature of the West and South coasts of South Africa. Five mass mortalities of West Coast rock lobsterJasus lalandii, including three of the most severe ever recorded in South Africa, occurred in the 1990s and resulted in the stranding of about 2263 tonnes of lobster. The bulk (97%) of the loss occurred in the last three years of the decade. The five events occurred within an 80 km stretch of coastline that straddled two fishing zones and resulted from hypoxic conditions associated with highbiomass dinoflagellate blooms. In each case, the quantity of lobsters stranded was directly related to the extent or duration of low-oxygen conditions. Small females constituted the bulk of the lobster stranded in most events. The lobster fisheries in the affected fishing zones suffered severe impacts. Recovery in one zone appears to be extremely slow, whereas the other zone is more resilient. Not only would a continuation of the trend of increasing frequency and severity of lobster strandings devastate the rock-lobster fishing industry and the employment prospects of small fishing communities, but it could also seriously affect the ecology of the region.

scholarly journals The Response of Macrophages and Neutrophils to Hypoxia in the Context of Cancer and Other Inflammatory Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Antje Egners ◽  
Merve Erdem ◽  
Thorsten Cramer
Keyword(s):  
Endothelial Cells ◽  
Inflammatory Diseases ◽  
Neutrophil Function ◽  
Proper Function ◽  
Low Oxygen ◽  
Bacterial Killing ◽  
Molecular Responses ◽  
Chronic Inflammatory Diseases ◽  
Hypoxic Conditions ◽  
Cellular Components

Lack of oxygen (hypoxia) is a hallmark of a multitude of acute and chronic diseases and can be either beneficial or detrimental for organ restitution and recovery. In the context of inflammation, hypoxia is particularly important and can significantly influence the course of inflammatory diseases. Macrophages and neutrophils, the chief cellular components of innate immunity, display distinct properties when exposed to hypoxic conditions. Virtually every aspect of macrophage and neutrophil function is affected by hypoxia, amongst others, morphology, migration, chemotaxis, adherence to endothelial cells, bacterial killing, differentiation/polarization, and protumorigenic activity. Prominent arenas of macrophage and neutrophil function, for example, acute/chronic inflammation and the microenvironment of solid tumors, are characterized by low oxygen levels, demonstrating the paramount importance of the hypoxic response for proper function of these cells. Members of the hypoxia-inducible transcription factor (HIF) family emerged as pivotal molecular regulators of macrophages and neutrophils. In this review, we will summarize the molecular responses of macrophages and neutrophils to hypoxia in the context of cancer and other chronic inflammatory diseases and discuss the potential avenues for therapeutic intervention that arise from this knowledge.

Mesozooplankton community in a seasonally hypoxic and highly eutrophic bay

2015 ◽  
Vol 66 (8) ◽  
pp. 719 ◽  
Author(s):  
Min-Chul Jang ◽  
Kyoungsoon Shin ◽  
Pung-Guk Jang ◽  
Woo-Jin Lee ◽  
Keun-Hyung Choi
Keyword(s):  
High Temperature ◽  
Bottom Water ◽  
Oxygen Solubility ◽  
Low Oxygen ◽  
Negative Effects ◽  
Mesozooplankton Community ◽  
Seawater Chemistry ◽  
Hypoxic Conditions ◽  
Bottom Waters ◽  
Major Factors

A 2-year survey of seawater chemistry and mesozooplankton abundance was carried out in Masan Bay, South Korea, one of the most eutrophic coastal ecosystems known. The study aimed to identify the major factors contributing to the seasonally persistent hypoxia in the bay, to characterise the Bay’s mesozooplankton community and to examine the effects of low oxygen on the distribution of mesozooplankton. Hypoxia (<2mgO2L–1) was present only in summer, with ultrahypoxia (<0.2mg O2 L–1) in the bottom waters of the inner bay in both years. Low summer oxygen can be attributed to high summer phytoplankton stocks, together with reduced oxygen solubility at high temperature and stratification of the water column that limits downward diffusion of oxygen. A seasonally and spatially distinct mesozooplankton community was identified in summer when there was greater influence of freshwater discharge in the inner bay. Marine cladocerans were very abundant, with a population outburst of Penilia avirostris in the inner bay (>4000 individuals m–3) during summer. During hypoxic events, the abundance of Penilia avirostris was positively related to oxygen levels in the bottom water, suggesting that hypoxic conditions may cause mortality or have sublethal negative effects on population growth of this filter-feeding cladoceran.

scholarly journals Design, Synthesis and Biological Evaluation of Novel 4-Substituted Coumarin Derivatives as Antitumor Agents

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2281 ◽  
Author(s):  
Ran An ◽  
Zhuang Hou ◽  
Jian-Teng Li ◽  
Hao-Nan Yu ◽  
Yan-Hua Mou ◽  
...  
Keyword(s):  
Antitumor Agents ◽  
Cancer Cell Line ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Hypoxic Conditions ◽  
Ca Ix ◽  
Ic50 Value ◽  
Almost All ◽  
New Compounds

Herein, fifteen new compounds containing coumarin, 1,2,3-triazole and benzoyl- substituted arylamine moieties were designed, synthesized and tested in vitro for their anticancer activity. The results showed that all tested compounds had moderate antiproliferative activity against MDA-MB-231, a human breast cancer cell line, under both normoxic and hypoxic conditions. Furthermore, the 4-substituted coumarin linked with benzoyl 3,4-dimethoxyaniline through 1,2,3-triazole (compound 5e) displayed the most prominent antiproliferative activities with an IC50 value of 0.03 μM, about 5000 times stronger than 4-hydroxycoumarin (IC50 > 100 μM) and 20 times stronger than doxorubicin (IC50 = 0.60 μM). Meanwhile, almost all compounds revealed general enhancement of proliferation-inhibiting activity under hypoxia, contrasted with normoxia. A docking analysis showed that compound 5e had potential to inhibit carbonic anhydrase IX (CA IX).

Enhancing the Mechanical Properties of Articular Cartilage Through Enzyme-Mediated Collagen Crosslinking as Regulated by Low Oxygen Tension

2012 ◽  
Author(s):  
Eleftherios A. Makris ◽  
Jerry Hu ◽  
Kyriacos A. Athanasiou
Keyword(s):  
Articular Cartilage ◽  
Oxygen Tension ◽  
Low Oxygen ◽  
Healthy Human ◽  
Collagen Crosslinking ◽  
Human Knee ◽  
Hypoxic Conditions ◽  
The Poor ◽  
Human Knee Joint ◽  
Low Oxygen Tension

The poor ability of articular cartilage to repair following disease and injury makes the tissue a key target for reparative and regenerative medicine strategies. It has been shown that human knee joint resides under hypoxic conditions. Oxygen tension in healthy human synovium is between 7 and 11% and in articular cartilage may therefore be as low as 1–2.5% [1].

Sign in / Sign up

Export Citation Format

Share Document