scholarly journals Assessment of hypoxia-inducible factor-1α mRNA expression in mantis shrimp as a biomarker of environmental hypoxia exposure

2011 ◽  
Vol 8 (2) ◽  
pp. 278-281 ◽  
Author(s):  
Keita Kodama ◽  
Md. Saydur Rahman ◽  
Toshihiro Horiguchi ◽  
Peter Thomas
Keyword(s):  
Hypoxia Inducible Factor ◽  
Cerebral Ganglion ◽  
Ecological Impacts ◽  
Tokyo Bay ◽  
Mrna Levels ◽  
Transcript Levels ◽  
Mantis Shrimp ◽  
Hypoxia Inducible Factor 1Α ◽  
Hypoxia Exposure ◽  
Environmental Hypoxia

Efforts to assess the ecological impacts of the marked increase in coastal hypoxia worldwide have been hampered by a lack of biomarkers of hypoxia exposure in marine benthic organisms. Here, we show that hypoxia-inducible factor-1α (HIF-1α) transcript levels in the heart and cerebral ganglion of mantis shrimp ( Oratosquilla oratoria ) collected from hypoxic sites in Tokyo Bay are elevated several-fold over those in shrimp collected from normoxic sites. Upregulation of HIF-1α mRNA levels in the heart after exposure to sub-lethal hypoxia was confirmed in controlled laboratory experiments. HIF-1α transcript levels were increased at approximately threefold after 7 and 14 days of hypoxia exposure and declined to control levels within 24 h of restoration to normoxic conditions. The results provide the first evidence for upregulation of HIF-1α transcript levels in two hypoxia-sensitive organs, heart and cerebral ganglion, in a marine invertebrate exposed to environmental hypoxia. These results suggest that upregulation of HIF-1α transcript levels is an important component in adaptation of mantis shrimp to chronic hypoxia and is a potentially useful biomarker of environmental hypoxia exposure.

scholarly journals Reduced liver fibrosis in hypoxia-inducible factor-1α-deficient mice

2009 ◽  
Vol 296 (3) ◽  
pp. G582-G592 ◽  
Author(s):  
Jeon-OK Moon ◽  
Timothy P. Welch ◽  
Frank J. Gonzalez ◽  
Bryan L. Copple
Keyword(s):  
Liver Fibrosis ◽  
Type I Collagen ◽  
Smooth Muscle Actin ◽  
Hypoxia Inducible Factor ◽  
Type I ◽  
Mrna Levels ◽  
Chronic Injury ◽  
Hypoxia Inducible Factor 1Α ◽  
Duct Ligation ◽  
Deficient Mice

Liver fibrosis is characterized by excessive deposition of extracellular matrix in the liver during chronic injury. During early stages of this disease, cells begin to synthesize and secrete profibrotic proteins that stimulate matrix production and inhibit matrix degradation. Although it is clear that these proteins are important for development of fibrosis, what remains unknown is the mechanism by which chronic liver injury stimulates their production. In the present study, the hypothesis was tested that hypoxia-inducible factor-1α (HIF-1α) is activated in the liver during chronic injury and regulates expression of profibrotic proteins. To investigate this hypothesis, mice were subjected to bile duct ligation (BDL), an animal model of liver fibrosis. HIF-1α protein was increased in the livers of mice subjected to BDL by 3 days after surgery. To test the hypothesis that HIF-1α is required for the development of fibrosis, control and HIF-1α-deficient mice were subjected to BDL. Levels of type I collagen and α-smooth muscle actin mRNA and protein were increased in control mice by 14 days after BDL. These levels were significantly reduced in HIF-1α-deficient mice. Next, the levels of several profibrotic mediators were measured to elucidate the mechanism by which HIF-1α promotes liver fibrosis. Platelet-derived growth factor (PDGF)-A, PDGF-B, and plasminogen activator inhibitor-1 mRNA levels were increased to a greater extent in control mice subjected to BDL compared with HIF-1α-deficient mice at 7 and 14 days after BDL. Results from these studies suggest that HIF-1α is a critical regulator of profibrotic mediator production during the development of liver fibrosis.

A single bout of exercise with high mechanical loading induces the expression of Cyr61/CCN1 and CTGF/CCN2 in human skeletal muscle

2007 ◽  
Vol 103 (4) ◽  
pp. 1395-1401 ◽  
Author(s):  
Riikka Kivelä ◽  
Heikki Kyröläinen ◽  
Harri Selänne ◽  
Paavo V. Komi ◽  
Heikki Kainulainen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Mechanical Loading ◽  
Human Skeletal Muscle ◽  
Hypoxia Inducible Factor ◽  
Tissue Growth ◽  
Vastus Lateralis Muscle ◽  
Ccn Proteins ◽  
Mrna Levels ◽  
Hypoxia Inducible Factor 1Α

High mechanical loading was hypothesized to induce the expression of angiogenic and/or lymphangiogenic extracellular matrix (ECM) proteins in skeletal muscle. Eight men performed a strenuous exercise protocol, which consisted of 100 unilateral maximal drop jumps followed by submaximal jumping until exhaustion. Muscle biopsies were taken 30 min and 48 h postexercise from the vastus lateralis muscle and analyzed for the following parameters: mRNA and protein expression of ECM-associated CCN proteins [cysteine-rich angiogenic protein 61 (Cyr61)/CCN1, connective tissue growth factor (CTGF)/CCN2], and mRNA expression of vascular endothelial growth factors (VEGFs) and hypoxia-inducible factor-1α. The mRNA expression of Cyr61 and CTGF increased 30 min after the exercise (14- and 2.5-fold, respectively; P < 0.001). Cyr61 remained elevated 48 h postexercise (threefold; P < 0.05). The mRNA levels of VEGF-A, VEGF-B, VEGF-C, VEGF-D, or hypoxia-inducible factor-1α did not change significantly at either 30 min or 48 h postexercise; however, the variation between subjects increased markedly in VEGF-A and VEGF-B mRNA. Cyr61 protein levels were higher at both 30 min and 48 h after the exercise compared with the control ( P < 0.05). Cyr61 and CTGF proteins were localized to muscle fibers and the surrounding ECM by immunohistochemistry. Fast fibers stained more intensively than slow fibers. In conclusion, mechanical loading induces rapid expression of CCN proteins in human skeletal muscle. This may be one of the early mechanisms involved in skeletal muscle remodeling after exercise, since Cyr61 and CTGF regulate the expression of genes involved in angiogenesis and ECM remodeling.

Oxidized low-density lipoprotein (oxLDL) triggers hypoxia-inducible factor-1α (HIF-1α) accumulation via redox-dependent mechanisms

Blood ◽  
2003 ◽  
Vol 101 (12) ◽  
pp. 4847-4849 ◽  
Author(s):  
Vladimir A. Shatrov ◽  
Vadim V. Sumbayev ◽  
Jie Zhou ◽  
Bernhard Brüne
Keyword(s):  
Reporter Gene ◽  
Low Density Lipoprotein ◽  
Hypoxia Inducible Factor ◽  
Density Lipoprotein ◽  
Luciferase Reporter ◽  
Low Density ◽  
Mrna Levels ◽  
Oxidized Low Density Lipoprotein ◽  
Human Macrophages ◽  
Hypoxia Inducible Factor 1Α

Abstract Oxidized low-density lipoprotein (oxLDL) and macrophages play a central role in atherosclerosis. Here, we obtained evidence that oxLDL induced hypoxia-inducible factor-1α (HIF-1α) protein accumulation in human macrophages (Mono-Mac-6) under normoxia. HIF-1α accumulation was attenuated by pretreatment with the antioxidant N-acetyl-L-cysteine (NAC), the nitric oxide (NO) donor S-nitrosoglutathione (GSNO), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors such as diphenyleniodonium (DPI) or 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF), thus implicating the contribution of oxLDL-generated reactive oxygen species (ROS). Whereas oxLDL did not modulate HIF-1α mRNA levels, experiments with cycloheximide pointed to a translational mechanism in oxLDL action. HIF-1–dependent luciferase reporter gene analysis underscored HIF-1 transactivation. Our results indicate that oxLDL induced HIF-1α accumulation and HIF-1–dependent reporter gene activation in human macrophages via a redox-mediated pathway. This finding may suggest a role of HIF-1 in atherosclerosis and oxLDL-induced pathogenesis.

scholarly journals RNA-Binding Proteins HuR and PTB Promote the Translation of Hypoxia-Inducible Factor 1α

2007 ◽  
Vol 28 (1) ◽  
pp. 93-107 ◽  
Author(s):  
Stefanie Galbán ◽  
Yuki Kuwano ◽  
Rudolf Pullmann ◽  
Jennifer L. Martindale ◽  
Hyeon Ho Kim ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
De Novo ◽  
Rna Binding Proteins ◽  
Hypoxia Inducible Factor ◽  
Mrna Levels ◽  
Entry Site ◽  
Hypoxia Inducible Factor 1Α ◽  
Ribonucleoprotein Complexes ◽  
Polypyrimidine Tract Binding Protein

ABSTRACT The levels of hypoxia-inducible factor 1α (HIF-1α) are tightly controlled. Here, we investigated the posttranscriptional regulation of HIF-1α expression in human cervical carcinoma HeLa cells responding to the hypoxia mimetic CoCl2. Undetectable in untreated cells, HIF-1α levels increased dramatically in CoCl2-treated cells, while HIF-1α mRNA levels were unchanged. HIF-1α translation was potently elevated by CoCl2 treatment, as determined by de novo translation analysis and by monitoring the polysomal association of HIF-1α mRNA. An internal ribosome entry site in the HIF-1α 5′ untranslated region (UTR) was found to enhance translation constitutively, but it did not further induce translation in response to CoCl2 treatment. Instead, we postulated that RNA-binding proteins HuR and PTB, previously shown to bind HIF-1α mRNA, participated in its translational upregulation after CoCl2 treatment. Indeed, both RNA-binding proteins were found to bind HIF-1α mRNA in a CoCl2-inducible manner as assessed by immunoprecipitation of endogenous ribonucleoprotein complexes. Using a chimeric reporter, polypyrimidine tract-binding protein (PTB) was found to bind the HIF-1α 3′UTR, while HuR associated principally with the 5′UTR. Lowering PTB expression or HuR expression using RNA interference reduced HIF-1α translation and expression levels but not HIF-1α mRNA abundance. Conversely, HIF-1α expression and translation in response to CoCl2 were markedly elevated after HuR overexpression. We propose that HuR and PTB jointly upregulate HIF-1α translation in response to CoCl2.

scholarly journals Effect of hindlimb unweighting on expression of hypoxia-inducible factor-1α vascular endothelial growth factor, angiopoietin, and their receptors in mouse skeletal muscle

2008 ◽  
pp. 613-620
Author(s):  
A Wagatsuma
Keyword(s):  
Skeletal Muscle ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Hypoxia Inducible Factor ◽  
Mrna Levels ◽  
Vascular Endothelial ◽  
Hindlimb Unweighting ◽  
Hypoxia Inducible Factor 1Α ◽  
Endothelial Growth Factor ◽  
Angiopoietin 1

Hindlimb unweighting (HU) leads to capillary regression in skeletal muscle. However, the molecular mechanism(s) remains to be elucidated. To gain insight into the regulation of this process, we investigated gene expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), angiopoietin, and their receptors in the atrophied muscle induced by HU. The hindlimbs of mice were unweighted by tailsuspension and then the gastrocnemius muscles were isolated after 10 days. To assess the capillary distribution, the capillary endothelium in frozen transverse sections was identified by staining for alkaline phosphatase. The mRNA levels were analyzed using a real-time reverse transcription-polymerase chain reaction. After 10 days of HU, the number of capillaries around a muscle fiber was significantly decreased by 19.5 %, suggesting that capillary regression appears to occur. The expression of HIF1α was significantly down-regulated after 10 days of HU. The expression of VEGF remained unchanged, whereas those of Flt-1, KDR/Flk-1, and neuropilin-1 were significantly down-regulated, suggesting that VEGF signaling through these receptors would be attenuated. The expression of angiopoietin-1, and -2, as well as their receptor, Tie-2 were also significantly down-regulated, suggesting that angiopoietin-1 signaling through Tie-2 would be attenuated. These findings suggest that alterations in expression of VEGF, angiopoietins, and their receptors may be associated with capillary regression after HU.

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