Hypoxia

Hypoxia interrupts the initiation of simian virus 40 (SV40) replication in vivo at a stage situated before unwinding of the origin region. After re-oxygenation, unwinding followed by a synchronous round of viral replication takes place. To further characterize the hypoxia-induced inhibition of unwinding, we analysed the binding of several replication proteins to the viral minichromosome before and after re-oxygenation.

11p research12 01-06-2013 41 4   Download

The search for endogenousdigitalishas led to the isolationof ouabain as well as several additional cardiotonic steroids of the cardenolide and bufadienolide type from blood, adre-nals, and hypothalamus.The concentration of endogenous ouabain is elevated in blood upon increased Na + uptake, hypoxia, and physical exercise.Changes in blood levels of ouabain upon physical exercise occur rapidly.

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It was shown previously [Riedinger, H. J., van Betteraey-Nikoleit, M & Probst, H. (2002)Eur. J. Biochem.269, 2383–2393] that initiation ofin vivo SV40 DNA replication is reversibly suppressed by hypoxia in a state where viral minichromosomes exhibit a nearly complete set of repli-cation proteins. Reoxygenation triggers fast completion and post-translational modifications.

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The effects of physiologically relevant hypoxia on the catalytic activity of cytochromecoxidase (CytOX), mito-chondrial gene expression, and both nuclear and mito-chondrial encoded CytOX mRNA levels were investigated in murine monocyte macrophages, mouse C2C12 skeletal myocytes and rat adrenal pheochromocytoma PC12 cells. Our results suggest a coordinated down regulation of mito-chondrial genome-coded CytOX I and II and nuclear genome-codedCytOX IV andVbmRNAs during hypoxia.

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To sustain life mammals have an absolute and continual requirement for oxygen, which is necessary to produce energy for normal cell survival and growth. Hence, main-tainingoxygen homeostasis is a critical requirement and mammals have evolved a wide range of cellular and phy-siological responses to adapt to changes in oxygen avail-ability. In the past few years it has become evident that the transcriptional protein complex hypoxia-inducible factor (HIF) is a key regulator of these processes.

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The transcription factor hypoxia inducible factora-subunit (HIFa)is pivotal in the cellular response to the stress of hypoxia. Post-translational modification of HIFa by hydroxylase enzymes has recently been identified as a key
oxygen sensing mechanism within the cell. The absence of the substrate oxygen prevents the hydroxylases from modi-fying HIFaduring hypoxia and allows dramatic up-regula-tion of both HIFaprotein stability and transcriptional activation capability.

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Glucose transporters (GLUTs) have been implicated in adaptive and survival responses to hypoxic stress in mam-mals. In fish, the expression and regulation ofGLUT in relation to hypoxia remains unexplored. Here we describe the identification ofa hypoxia-responsive glucose transpor-ter gene (gcGLUT) and the corresponding full-length cDNA from the grass carp. The gene spans
11 kb ofgenomic sequence and consists of12 exons and 11 introns, and an open reading frame (ORF) of 1599 bp encoding a poly-peptide of533 amino acids, with a predictedmolecularmass of
57 kDa and a pI of8.34....

8p fptmusic 16-04-2013 42 3   Download

The formation of disulfide bonds in the endoplasmic reti-culum requires protein disulfide isomerase (PDI) and endoplasmic reticulum oxidoreductin 1 (ERO1) that reoxi-dizes PDI. We report here that the expression of the rat, mouse andhumanhomologues ofERO1-Likeproteinabut not of the isoform ERO1-Lbare stimulated by hypoxia in rats vivo and in rat, mouse and human cell cultures.

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Post ischaemic cell calcium invasion has been described as one of the main causes of graft failure. Protective effects of calcium antagonists have been investigated but are not con-vincing and their mechanisms of action remain unclear. In this work we tested the protective effect of a new calcium inhibitor described to block a calcium current insensitive to all known calcium blockers. Specific mapacalcine receptors were first characterized on rat hepatocytesmembranes using the 125 I-labeledmapacalcine....

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The molecular response to hypoxia stress in aquatic invertebrates remains relatively unknown. In this study, we investigated the response of the Pacific oyster Crassostrea gigasto hypoxia under experimental conditions and focused on the analysis of the differential expression patterns of specific genes associated with hypoxia response. A suppression subtractive hybridiza-tion method was used to identify specific hypoxia up- and downregulated genes, in gills, mantle and digestive gland, after 7–10 days and 24 days of exposure....

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We examined whether the fast release of replicon initiation after sudden O2 recovery of hypoxically incubated mammalian cells depends on kinase activity of Cdk2. We used a system based on starved⁄refed T24 cells elab-orated previously for such investigations [van Betteraey-Nikoleit M, Eisele KH, Stabenow D & Probst H (2003)Eur J Biochem270, 3880–3890].

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In this study, we have characterized the influence of hypoxia on the expression of hydroxylases crucially involved in col-lagen fiber formation, such as prolyl-4-hydroxylases (Ph4) and procollagen lysyl-hydroxylases (PLOD). Using the rat vascular smooth muscle cell line A7r5, we found that an hypoxic atmosphere caused a characteristic time-dependent five- to 12-fold up-regulation of the mRNAs of the two P4h a-subunits [aI (P4ha1) andaII (P4ha2)] and of two lysyl-hydroxylases (PLOD1 and PLOD2).

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Fromin vivo models of stroke it is known that ischemia⁄reperfusion indu-ces oxidative stress that is accompanied by deterioration of brain mito-chondria. Previously, we reported that the increase in Ca 2+ induces functional breakdown and morphological disintegration in brain mitochon-dria subjected to hypoxia⁄reoxygenation (H⁄R). Protection by ADP indica-ted the involvement of the mitochondrial permeability transition pore in the mechanism of membrane permeabilization.

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The retinal pigment epithelium (RPE) is essential for main-tenance of photoreceptors and normally functions under conditions enriched with reactive oxygen species. RPE therefore expresses various defense enzymes against oxida-tive stress, including heme oxygenase-1 (HO-1). HO-1 catalyzes heme breakdown to release iron, carbon monox-ide, and biliverdin, which is reduced to bilirubin, a potent radical scavenger. HO-1 expression is induced by various environmental factors, which has been established as a def-ense mechanism....

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Injury of liver by ischaemia crucially involves mitochondrial damage. The role of Ca 2+ in mitochondrial damage is still unclear. We investigated the effect of low micromolar Ca 2+ concentrations on respiration, membrane permeability, and antioxidative defence in liver mitochondria exposed to hypoxia⁄reoxygenation. Hypoxia⁄reoxygenation caused decrease in state 3 respiration and in the respiratory control ratio.

9p dell39 27-03-2013 42 3   Download

Oxygen-binding globins occur in the nervous systems of both invertebrates and vertebrates. While the function of invertebrate nerve haemoglobins as oxygen stores that extend neural excitability under hypoxia has been con-vincingly demonstrated, the physiological role of vertebrate neuroglobins is less well understood.

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Heme oxygenase consists of two structurally related isozymes, heme oxyge-nase-1 and and heme oxygenase-2, each of which cleaves heme to form bili-verdin, iron and carbon monoxide. Expression of heme oxygenase-1 is increased or decreased depending on cellular microenvironments, whereas lit-tle is known about the regulation of heme oxygenase-2 expression.

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Although essentially unknown, several functions are hypothesized for neu-roglobin and cytoglobin, two new members of the globin family. In this article, we try to shed more light on their possible roles in hypoxia and detoxification of reactive oxygen speciesin vivo. Thijs

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Iron regulatory protein-1 binding to the iron-responsive element of mRNA is sensitive to iron, oxidative stress, NO, and hypoxia. Each of these agents changes the level of intracellular ATP, suggesting a link between iron levels and cellular energy metabolism.

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Goldfish (Carassius auratus) may survive in aquatic environments with low oxygen partial pressures. We investigated the contribution of respiratory proteins to hypoxia tolerance inC. auratus. We determined the complete coding sequence of hemoglobinaandband myoglobin, as well as partial cDNAs from neuroglobin and cytoglobin.

11p galaxyss3 07-03-2013 31 3   Download