Evolution of the coordinate regulation of glycolytic enzyme genes by hypoxia

Webster, Keith A.

doi:10.1242/jeb.00516

Cited by 149 publications

(125 citation statements)

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“…It has been suggested that glycolytic enzymes in a variety of organisms are coordinately upregulated during hypoxic stress (Webster, 2003). Our data do not support a simple interpretation of this hypothesis, which predicts increased levels of all glycolytic enzymes in a given tissue during hypoxia.…”

Section: Variation Within the Glycolytic Pathwaycontrasting

confidence: 99%

Effects of long-term hypoxia on enzymes of carbohydrate metabolism in the Gulf killifish,Fundulus grandis

Martínez

Landry

Boehm

et al. 2006

Journal of Experimental Biology

104

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SUMMARY The goal of the current study was to generate a comprehensive, multi-tissue perspective of the effects of chronic hypoxic exposure on carbohydrate metabolism in the Gulf killifish Fundulus grandis. Fish were held at approximately 1.3 mg l-1 dissolved oxygen (∼3.6 kPa) for 4 weeks, after which maximal activities were measured for all glycolytic enzymes in four tissues (white skeletal muscle, liver, heart and brain), as well as for enzymes of glycogen metabolism (in muscle and liver) and gluconeogenesis(in liver). The specific activities of enzymes of glycolysis and glycogen metabolism were strongly suppressed by hypoxia in white skeletal muscle, which may reflect decreased energy demand in this tissue during chronic hypoxia. In contrast, several enzyme specific activities were higher in liver tissue after hypoxic exposure, suggesting increased capacity for carbohydrate metabolism. Hypoxic exposure affected fewer enzymes in heart and brain than in skeletal muscle and liver, and the changes were smaller in magnitude, perhaps due to preferential perfusion of heart and brain during hypoxia. The specific activities of some gluconeogenic enzymes increased in liver during long-term hypoxic exposure, which may be coupled to increased protein catabolism in skeletal muscle. These results demonstrate that when intact fish are subjected to prolonged hypoxia, enzyme activities respond in a tissue-specific fashion reflecting the balance of energetic demands, metabolic role and oxygen supply of particular tissues. Furthermore, within glycolysis, the effects of hypoxia varied among enzymes, rather than being uniformly distributed among pathway enzymes.

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Section: Variation Within the Glycolytic Pathwaycontrasting

confidence: 99%

Effects of long-term hypoxia on enzymes of carbohydrate metabolism in the Gulf killifish,Fundulus grandis

Martínez

Landry

Boehm

et al. 2006

Journal of Experimental Biology

104

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“…Since the activation of HIFs did not contribute to the detected upregulation of HCV replication at 3% O 2 , we examined global cellular gene expression changes in mock-and JFH1/adpt1-infected Huh7.5 cells using hypoxia signaling pathway-focused DNA microarrays. Cells cultured for 24 h at 3% O 2 showed (18,47) an upregulation (by at least 2-fold) of several hypoxia-related genes (see Table S2 in the supplemental material), such as HIFs, directing transcriptional targets (VEGFA, EPO), genes encoding stress-related proteins, and genes involved in oxidative stress and reactive oxygen species (ROS) production, glucose transport (GLUT1, GLUT8) and metabolism (HK2, ENO1), cell growth, proliferation, and cell cycle regulation, including the FOS, MYCN, and KIT oncogenes. Notably, the respective transcript levels in uninfected and infected cells were similar.…”

Section: Resultsmentioning

confidence: 99%

Low Oxygen Tension Enhances Hepatitis C Virus Replication

Vassilaki

Kalliampakou

Kotta‐Loizou

et al. 2013

J Virol

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; Applied Molecular Virology, Institut Pasteur Korea, Seongnam-si, South Korea g Low oxygen tension exerts a significant effect on the replication of several DNA and RNA viruses in cultured cells. In vitro propagation of hepatitis C virus (HCV) has thus far been studied under atmospheric oxygen levels despite the fact that the liver tissue microenvironment is hypoxic. In this study, we investigated the efficiency of HCV production in actively dividing or differentiating human hepatoma cells cultured under low or atmospheric oxygen tensions. By using both HCV replicons and infectionbased assays, low oxygen was found to enhance HCV RNA replication whereas virus entry and RNA translation were not affected. Hypoxia signaling pathway-focused DNA microarray and real-time quantitative reverse transcription-PCR (qRT-PCR) analyses revealed an upregulation of genes related to hypoxic stress, glycolytic metabolism, cell growth, and proliferation when cells were kept under low (3% [vol/vol]) oxygen tension, likely reflecting cell adaptation to anaerobic conditions. Interestingly, hypoxia-mediated enhancement of HCV replication correlated directly with the increase in anaerobic glycolysis and creatine kinase B (CKB) activity that leads to elevated ATP production. Surprisingly, activation of hypoxia-inducible factor alpha (HIF-␣) was not involved in the elevation of HCV replication. Instead, a number of oncogenes known to be associated with glycolysis were upregulated and evidence that these oncogenes contribute to hypoxia-mediated enhancement of HCV replication was obtained. Finally, in liver biopsy specimens of HCV-infected patients, the levels of hypoxia and anaerobic metabolism markers correlated with HCV RNA levels. These results provide new insights into the impact of oxygen tension on the intricate HCVhost cell interaction. H epatitis C virus (HCV) infection causes a wide range of clinical manifestations, from a healthy carrier state to acute and chronic hepatitis that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Nearly 3% of the world's population is chronically infected with HCV (1, 2), and current therapeutic approaches are not broadly effective (3).HCV is a positive-strand RNA virus with a 9.6-kb genome that is flanked at both termini by conserved, nontranslated regions (NTRs), required for RNA translation and replication. The 5= NTR comprises an internal ribosome entry site (IRES) that directs the expression of a polyprotein precursor (4, 5). The polyprotein is cleaved into structural (core, E1, E2) and nonstructural (p7, NS2, NS3, NS4A, NS4B, NS5A, NS5B) proteins that, in association with cellular factors, form a membrane-associated replicase complex. This copies the viral positive-strand RNA into a negative-strand intermediate that serves as the template for the synthesis of progeny genomes. The alternative reading frame (ARFP) or coreϩ1 and minicore proteins, with as-yet-unknown functions, appear to be synthesized from the core region by alternative translation mechanisms (6, 7).Studies of the...

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“…43 The expression of a number of hypoxia 'marker genes' is reliably increased or decreased in conditions leading to oxidative damage: hypoxia has been shown to trigger the phosphorylation of constitutively expressed hypoxia-inducible factors (HIFs) directly leading to an increased antioxidant response (to mop-up ROS) and altered expression of glycolytic and oxidative phosphorylation proteins. 44 Two hypoxia-inducible factors (HIF3a and HIF-1b) were significantly increased at the transcript level in the schizophrenia prefrontal cortex.…”

Section: Hypoxiamentioning

confidence: 99%

Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress

et al. 2004

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The etiology and pathophysiology of schizophrenia remain unknown. A parallel transcriptomics, proteomics and metabolomics approach was employed on human brain tissue to explore the molecular disease signatures. Almost half the altered proteins identified by proteomics were associated with mitochondrial function and oxidative stress responses. This was mirrored by transcriptional and metabolite perturbations. Cluster analysis of transcriptional alterations showed that genes related to energy metabolism and oxidative stress differentiated almost 90% of schizophrenia patients from controls, while confounding drug effects could be ruled out. We propose that oxidative stress and the ensuing cellular adaptations are linked to the schizophrenia disease process and hope that this new disease concept may advance the approach to treatment, diagnosis and disease prevention of schizophrenia and related syndromes.

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Evolution of the coordinate regulation of glycolytic enzyme genes by hypoxia

Cited by 149 publications

References 100 publications

Effects of long-term hypoxia on enzymes of carbohydrate metabolism in the Gulf killifish,Fundulus grandis

Effects of long-term hypoxia on enzymes of carbohydrate metabolism in the Gulf killifish,Fundulus grandis

Low Oxygen Tension Enhances Hepatitis C Virus Replication

Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress

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