Differential gene expression indicates modulated responses to chronic and intermittent hypoxia in corallivorous fireworms (Hermodice carunculata)

AbstractClimate models predict an increase in extent, frequency, and duration of marine hypoxia events in the twenty first century. A better understanding of organismal responses to hypoxia in individual species is a crucial step for predicting ecosystem responses. We experimentally subjected a common invertebrate, the bearded fireworm (Hermodice carunculata) to two levels of chronic hypoxia and, in a separate experiment, to intermittent hypoxia. We found components of the conserved hypoxia-inducible factor (HIF) pathway and show a modulated response to hypoxia depending on the severity of hypoxic stress: under mild hypoxia, only the HIF-1α subunit is upregulated, while expression of the other subunit, aryl hydrocarbon nuclear translator, only increases significantly at more severe hypoxia levels. The chronic trials revealed down-regulation of genes related to cell adhesion, transport, development and heme-binding, and up-regulation of genes related to glycolysis, oxygen binding, cell differentiation, digestive and reproductive function. The intermittent hypoxia trials revealed an upregulation of heme transporter activity during hypoxia, and our time series analysis characterized nine clusters of genes with similar expression patterns. Our findings suggest that H. carunculata is likely to tolerate, and be resilient to, predicted future hypoxia conditions.

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Effects of Melatonin on Peripheral Reproductive Function: Regulation of Testicular GnIH and Testosterone

Endocrinology ◽

10.1210/en.2011-1053 ◽

2011 ◽

Vol 152 (9) ◽

pp. 3461-3470 ◽

Cited By ~ 57

Author(s):

Nicolette L. McGuire ◽

Kristina Kangas ◽

George E. Bentley

Keyword(s):

Expression Patterns ◽

Reproductive Function ◽

Melatonin Receptors ◽

Sex Steroid ◽

European Starlings ◽

Steroid Secretion ◽

Local Inhibition ◽

Gonadotropin Inhibitory Hormone ◽

The Brain

Study of seasonal reproduction has focused on the brain. Here, we show that the inhibition of sex steroid secretion can be seasonally mediated at the level of the gonad. We investigate the direct effects of melatonin on sex steroid secretion and gonadal neuropeptide expression in European starlings (Sturnus vulgaris). PCR reveals starling gonads express mRNA for gonadotropin inhibitory hormone (GnIH) and its receptor (GnIHR) and melatonin receptors 1B (Mel 1B) and 1C (Mel 1C). We demonstrate that the gonadal GnIH system is regulated seasonally, possibly via a mechanism involving melatonin. GnIH/ GnIHR expression in the testes is relatively low during breeding compared with outside the breeding season. The expression patterns of Mel 1B and Mel 1C are correlated with this expression, and melatonin up-regulates the expression of GnIH mRNA in starling gonads before breeding. In vitro, GnIH and melatonin significantly decrease testosterone secretion from LH/FSH-stimulated testes before, but not during, breeding. Thus local inhibition of sex steroid secretion appears to be regulated seasonally at the level of the gonad, by a mechanism involving melatonin and the gonadal GnIH system.

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Hypoxia-inducible factor-1α and vascular endothelial growth factor in the cardioprotective effects of intermittent hypoxia in rats

Upsala Journal of Medical Sciences ◽

10.3109/03009734.2013.766914 ◽

2013 ◽

Vol 118 (2) ◽

pp. 65-74 ◽

Cited By ~ 16

Author(s):

Zhang Wang ◽

Liang-Yi Si

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Intermittent Hypoxia ◽

Hypoxia Inducible Factor ◽

Vascular Endothelial ◽

Hypoxia Inducible Factor 1Α ◽

Cardioprotective Effects ◽

Endothelial Growth Factor

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Expression of MTDH and IL-10 Is an Independent Predictor of Worse Prognosis in ER-Negative or PR-Negative Breast Cancer Patients

Journal of Clinical Medicine ◽

10.3390/jcm9103153 ◽

2020 ◽

Vol 9 (10) ◽

pp. 3153

Author(s):

Pei-Yi Chu ◽

Shin-Mae Wang ◽

Po-Ming Chen ◽

Feng-Yao Tang ◽

En-Pei Isabel Chiang

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Mrna Expression ◽

Cancer Patients ◽

Expression Patterns ◽

Hypoxia Inducible Factor ◽

Tumor Hypoxia ◽

Tissue Microarrays ◽

Breast Cancer Patients ◽

Worse Prognosis

(1) Background: Tumor hypoxia leads to metastasis and certain immune responses, and interferes with normal biological functions. It also affects glucose intake, down-regulates oxidative phosphorylation, and inhibits fatty-acid desaturation regulated by hypoxia-inducible factor 1α (HIF-1α). Although tumor hypoxia has been found to promote tumor metastasis, the roles of HIF-1α-regulated genes and their application are not completely integrated in clinical practice. (2) Methods: We examined the correlation between HIF-1α, metadherin (MTDH), and interleukin (IL)-10 mRNA expression, as well as their expression patterns in the prognosis of breast cancer using the Gene Expression Profiling Interactive Analysis (GEPIA) databases via a web interface; tissue microarrays (TMAs) were stained for MTDH and IL-10 protein expression using immunohistochemistry. (3) Results: HIF-1α, MTDH, and IL-10 mRNA expression are highly correlated and strongly associated with poor prognosis. MTDH and IL-10 protein expression of breast cancer patients usually harbored negative estrogen receptor (ER) or progesterone receptor (PR) status, and late-stage tumors have higher IL-10 expression. With regard to MTDH and IL-10 protein expression status for using univariate and multivariate analysis, the results showed that the protein expression of MTDH and IL-10 in ER-negative or PR-negative breast cancer patients have the worse prognosis. (4) Conclusions: we propose a new insight into hypoxia tumors in the metabolism and immune evidence for breast cancer therapy.

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Accelerated tumor growth under intermittent hypoxia is associated with hypoxia-inducible factor-1-dependent adaptive responses to hypoxia

Oncotarget ◽

10.18632/oncotarget.18644 ◽

2017 ◽

Vol 8 (37) ◽

pp. 61592-61603 ◽

Cited By ~ 15

Author(s):

Dae Wui Yoon ◽

Daeho So ◽

Sra Min ◽

Jiyoung Kim ◽

Mingyu Lee ◽

...

Keyword(s):

Tumor Growth ◽

Intermittent Hypoxia ◽

Hypoxia Inducible Factor ◽

Adaptive Responses ◽

Hypoxia Inducible Factor 1

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Models of intermittent hypoxia and obstructive sleep apnea: molecular pathways and their contribution to cancer

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00036.2018 ◽

2018 ◽

Vol 315 (4) ◽

pp. R669-R687 ◽

Cited By ~ 24

Author(s):

Imre Hunyor ◽

Kristina M. Cook

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Intermittent Hypoxia ◽

Inflammatory Responses ◽

Hypoxia Inducible Factor ◽

Small Animal ◽

Molecular Pathways ◽

Significant Heterogeneity ◽

Obstructive Sleep

Obstructive sleep apnea (OSA) is common and linked to a variety of poor health outcomes. A key modulator of this disease is nocturnal intermittent hypoxia. There is striking epidemiological evidence that patients with OSA have higher rates of cancer and cancer mortality. Small-animal models demonstrate an important role for systemic intermittent hypoxia in tumor growth and metastasis, yet the underlying mechanisms are poorly understood. Emerging data indicate that intermittent hypoxia activates the hypoxic response and inflammatory pathways in a manner distinct from chronic hypoxia. However, there is significant heterogeneity in published methods for modeling hypoxic conditions, which are often lacking in physiological relevance. This is particularly important for studying key transcriptional mediators of the hypoxic and inflammatory responses such as hypoxia-inducible factor (HIF) and NF-κB. The relationship between HIF, the molecular clock, and circadian rhythm may also contribute to cancer risk in OSA. Building accurate in vitro models of intermittent hypoxia reflective of OSA is challenging but necessary to better elucidate underlying molecular pathways.

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Strong iron demand during hypoxia-induced erythropoiesis is associated with down-regulation of iron-related proteins and myoglobin in human skeletal muscle

Blood ◽

10.1182/blood-2006-08-040006 ◽

2007 ◽

Vol 109 (11) ◽

pp. 4724-4731 ◽

Cited By ~ 79

Author(s):

Paul Robach ◽

Gaetano Cairo ◽

Cecilia Gelfi ◽

Francesca Bernuzzi ◽

Henriette Pilegaard ◽

...

Keyword(s):

Skeletal Muscle ◽

Iron Content ◽

Iron Homeostasis ◽

Iron Acquisition ◽

Hypoxia Inducible Factor ◽

Hemoglobin Concentration ◽

Oxygen Binding ◽

Mrna Levels ◽

Iron Regulatory Proteins ◽

Related Proteins

Abstract Iron is essential for oxygen transport because it is incorporated in the heme of the oxygen-binding proteins hemoglobin and myoglobin. An interaction between iron homeostasis and oxygen regulation is further suggested during hypoxia, in which hemoglobin and myoglobin syntheses have been reported to increase. This study gives new insights into the changes in iron content and iron-oxygen interactions during enhanced erythropoiesis by simultaneously analyzing blood and muscle samples in humans exposed to 7 to 9 days of high altitude hypoxia (HA). HA up-regulates iron acquisition by erythroid cells, mobilizes body iron, and increases hemoglobin concentration. However, contrary to our hypothesis that muscle iron proteins and myoglobin would also be up-regulated during HA, this study shows that HA lowers myoglobin expression by 35% and down-regulates iron-related proteins in skeletal muscle, as evidenced by decreases in L-ferritin (43%), transferrin receptor (TfR; 50%), and total iron content (37%). This parallel decrease in L-ferritin and TfR in HA occurs independently of increased hypoxia-inducible factor 1 (HIF-1) mRNA levels and unchanged binding activity of iron regulatory proteins, but concurrently with increased ferroportin mRNA levels, suggesting enhanced iron export. Thus, in HA, the elevated iron requirement associated with enhanced erythropoiesis presumably elicits iron mobilization and myoglobin down-modulation, suggesting an altered muscle oxygen homeostasis.

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Adaptive and Maladaptive Cardiorespiratory Responses to Continuous and Intermittent Hypoxia Mediated by Hypoxia-Inducible Factors 1 and 2

Physiological Reviews ◽

10.1152/physrev.00030.2011 ◽

2012 ◽

Vol 92 (3) ◽

pp. 967-1003 ◽

Cited By ~ 311

Author(s):

Nanduri R. Prabhakar ◽

Gregg L. Semenza

Keyword(s):

Transcriptional Activation ◽

Intermittent Hypoxia ◽

Hypoxia Inducible Factor ◽

Metabolic Reprogramming ◽

Hypoxia Inducible Factor 1 ◽

Oxygen Homeostasis ◽

Physiological Adaptations ◽

Prolyl Hydroxylation ◽

Insight Into ◽

Subsequent Identification

Hypoxia is a fundamental stimulus that impacts cells, tissues, organs, and physiological systems. The discovery of hypoxia-inducible factor-1 (HIF-1) and subsequent identification of other members of the HIF family of transcriptional activators has provided insight into the molecular underpinnings of oxygen homeostasis. This review focuses on the mechanisms of HIF activation and their roles in physiological and pathophysiological responses to hypoxia, with an emphasis on the cardiorespiratory systems. HIFs are heterodimers comprised of an O2-regulated HIF-1α or HIF-2α subunit and a constitutively expressed HIF-1β subunit. Induction of HIF activity under conditions of reduced O2availability requires stabilization of HIF-1α and HIF-2α due to reduced prolyl hydroxylation, dimerization with HIF-1β, and interaction with coactivators due to decreased asparaginyl hydroxylation. Stimuli other than hypoxia, such as nitric oxide and reactive oxygen species, can also activate HIFs. HIF-1 and HIF-2 are essential for acute O2sensing by the carotid body, and their coordinated transcriptional activation is critical for physiological adaptations to chronic hypoxia including erythropoiesis, vascularization, metabolic reprogramming, and ventilatory acclimatization. In contrast, intermittent hypoxia, which occurs in association with sleep-disordered breathing, results in an imbalance between HIF-1α and HIF-2α that causes oxidative stress, leading to cardiorespiratory pathology.

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Induction of the HIF pathway: Differential regulation by chemical hypoxia and oxygen glucose deprivation

10.1101/525006 ◽

2019 ◽

Author(s):

Alicia E. Novak ◽

Susan M. Jones ◽

J. Paul Elliott

Keyword(s):

Transcriptional Activation ◽

Cellular Response ◽

Target Genes ◽

Expression Patterns ◽

Hypoxia Inducible Factor ◽

Glucose Deprivation ◽

Oxygen Glucose Deprivation ◽

Oxygen Levels ◽

Chemical Hypoxia ◽

Hif Pathway

AbstractThe Hypoxia Inducible Factor (HIF) proteins are the master regulators in the cellular response to varying oxygen levels, including hypoxia. The HIF complex is stabilized and accumulates when oxygen levels drop through inhibition of a degradative enzyme. An active HIF complex can act as a transcriptional regulator of hundreds of genes. In turn, these genes determine the response of the cell by inducing pathways which can promote survival, or result in cell death. However, little is known about the regulation of the transcriptional process. We were interested in learning more about the time dependence of transcriptional activation in order to target those pathways which could enhance cell survival after ischemia. Using mouse hippocampal organotypic cultures (HOTCs), we compared oxygen-glucose deprivation with the hypoxia mimetic cobalt, which inhibits the oxygen dependent prolyl hydroylase and blocks degradation of the HIF proteins. We demonstrated that two of the most studied HIF target genes (VEGF, EPO) as well as HIF structural genes show complex time and dose-dependent expression patterns in response to the two different insults. Understanding of these molecular responses is crucial for the development of future treatments to enhance recovery from hypoxia and stroke.

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Aerosol absorption in global models from AeroCom Phase III

10.5194/acp-2021-51 ◽

2021 ◽

Author(s):

Maria Sand ◽

Bjørn H. Samset ◽

Gunnar Myhre ◽

Jonas Gliß ◽

Susanne E. Bauer ◽

...

Keyword(s):

Phase Ii ◽

Climate Models ◽

Global Climate ◽

Global Climate Models ◽

Phase Iii ◽

Shortwave Radiation ◽

Cloud Formation ◽

Individual Species ◽

Aerosol Absorption ◽

The Difference

Abstract. Aerosol induced absorption of shortwave radiation can modify the climate through local atmospheric heating, which affects lapse rates, precipitation, and cloud formation. Presently, the total amount of such absorption is poorly constrained, and the main absorbing aerosol species (black carbon (BC), organic aerosols (OA) and mineral dust are diversely quantified in global climate models. As part of the third phase of the AeroCom model intercomparison initiative (AeroCom Phase III) we here document the distribution and magnitude of aerosol absorption in current global aerosols models and quantify the sources of intermodel spread. 15 models have provided total present-day absorption at 550 nm, and 11 of these models have provided absorption per absorbing species. The multi-model global annual mean total absorption aerosol optical depth (AAOD) is 0.0056 [0.0020 to 0.0097] (550 nm) with range given as the minimum and maximum model values. This is 31 % higher compared to 0.0042 [0.0021 to 0.0076] in AeroCom Phase II, but the difference/increase is within one standard deviation which in this study is 0.0024 (0.0019 in Phase II). The models show considerable diversity in absorption. Of the summed component AAOD, 57 % (range 34–84 %) is estimated to be due to BC, 30 % (12–49 %) is due to dust and 14 % (4–49 %) is due to OA, however the components are not entirely independent. Models with the lowest BC absorption tend to have the highest OA absorption, which illustrates the complexities in separating the species. The geographical distribution of AAOD between the models varies greatly and reflects the spread in global mean AAOD and in the relative contributions from individual species. The optical properties of BC are recognized as a large source of uncertainty. The model mean BC mass absorption coefficient (MACBC) value is 9.8 [3.1 to 16.6] m2 g−1 (550 nm). Observed MAC values from various locations range between 5.7–20.0 m2 g−1 (550 nm). Compared to retrievals of AAOD and absorption Ångstrøm exponent (AAE) from ground-based observations from the Aerosol Robotic Network (AERONET) stations, most models underestimate total AAOD and AAE. The difference in spectral dependency between the models is striking.

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