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Low Oxygen Tension (low + oxygen_tension)

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Medical Sciences60%

Selected Abstracts

Lowering oxygen tension enhances the differentiation of mouse embryonic stem cells into neuronal cells

BIOTECHNOLOGY PROGRESS, Issue 5 2009
Paul Mondragon-Teran
Abstract Embryonic stem cells (ESC) are capable of proliferating indefinitely in vitro whilst retaining their ability to differentiate into cells of every adult lineage. Efficient, high yield processes, which direct differentiation of ESC to specific lineages, will underpin the development of cost-effective drug screening and cell therapy products. The aim of this study was to investigate whether laboratory oxygen tension currently used for the neuronal differentiation of ESC was suboptimal resulting in inefficient process yields. An adherent monolayer protocol for the neuronal differentiation of mouse ESC (mESC) was performed in oxygen controlled chambers using a chemically defined media over an 8 day period of culture. When exposed to oxygen tensions more appropriate to in vivo neuronal development (2% O2), there was a 34-fold increase in the yield of viable cells from the differentiation process. Low oxygen tension inhibited cell death during an early phase (48 to 96 h) and toward the end (120 to 192 h) of the process. The percentage of cells expressing neuronal markers was determined by flow cytometry, revealing a small rise in the ,III tubulin and a threefold increase in the MAP2 populations at 2% O2. The total increase in the yield of viable cells expressing neuronal markers was shown to be 55-fold for ,III tubulin and 114-fold for MAP2. In conclusion, this study revealed that low oxygen tension can be used to enhance the yield of neuronal cells derived from ESCs and has implications for the development of efficient, cost-effective production processes. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source]

The Physiology of Endothelial Xanthine Oxidase: From Urate Catabolism to Reperfusion Injury to Inflammatory Signal Transduction

MICROCIRCULATION, Issue 3 2002
AVEDIS MENESHIAN
ABSTRACT Xanthine oxidoreductase (XOR) is a ubiquitous metalloflavoprotein that appears in two interconvertible yet functionally distinct forms: xanthine dehydrogenase (XD), which is constitutively expressed in vivo; and xanthine oxidase (XO), which is generated by the posttranslational modification of XD, either through the reversible, incremental thiol oxidation of sulfhydryl residues on XD or the irreversible proteolytic cleavage of a segment of XD, which occurs at low oxygen tension and in the presence of several proinflammatory mediators. Functionally, both XD and XO catalyze the oxidation of purines to urate. However, whereas XD requires NAD+ as an electron acceptor for these redox reactions, thereby generating the stable product NADH, XO is unable to use NAD+ as an electron acceptor, requiring instead the reduction of molecular oxygen for this purine oxidation and generating the highly reactive superoxide free radical. Nearly 100 years of study has documented the physiologic role of XD in urate catabolism. However, the rapid, posttranslational conversion of XD to the oxidantgenerating form XO provides a possible physiologic mechanism for rapid, posttranslational, oxidant-mediated signaling. XO-generated reactive oxygen species (ROS) have been implicated in various clinicopathologic entities, including ischemia/reperfusion injury and multisystem organ failure. More recently, the concept of physiologic signal transduction mediated by ROS has been proposed, and the possibility of XD to XO conversion, with subsequent ROS generation, serving as the trigger of the microvascular inflammatory response in vivo has been hypothesized. This review presents the evidence and basis for this hypothesis. [source]

Hypoxia-inducible factor 1, inhibits the fibroblast-like markers type I and type III collagen during hypoxia-induced chondrocyte redifferentiation: Hypoxia not only induces type II collagen and aggrecan, but it also inhibits type I and type III collagen in the hypoxia-inducible factor 1,,dependent redifferentiation of chondrocytes

ARTHRITIS & RHEUMATISM, Issue 10 2009
Elise Duval
Objective Autologous chondrocyte implantation requires expansion of cells ex vivo, leading to dedifferentiation of chondrocytes (loss of aggrecan and type II collagen to the profit of type I and type III collagens). Several approaches have been described for redifferentiation of these cells. Among them, low oxygen tension has been exploited to restore the differentiated chondrocyte phenotype, but molecular mechanisms of this process remain unclear. However, under conditions of hypoxia, one of the major factors involved is hypoxia-inducible factor 1, (HIF-1,). The purpose of this study was to investigate the role of HIF-1, during human chondrocyte redifferentiation. Methods We used complementary approaches to achieving HIF-1, loss (inhibition by cadmium ions and dominant-negative expression) or gain (ectopic expression and cobalt ion treatment) of function. Expression of chondrocyte, as well as fibroblast-like, phenotype markers was determined using real-time reverse transcription,polymerase chain reaction and Western blot analyses. Binding activities of HIF-1, and SOX9, a pivotal transcription factor of chondrogenesis, were evaluated by electrophoretic mobility shift assays and by chromatin immunoprecipitation assay. Results We found that hypoxia and HIF-1, not only induced the expression of SOX9, COL2A1, and aggrecan, but they simultaneously inhibited the expression of COL1A1, COL1A2, and COL3A1. In addition, we identified the binding of HIF-1, to the aggrecan promoter, the first such reported demonstration of this binding. Conclusion This study is the first to show a bimodal role of HIF-1, in cartilage homeostasis, since HIF-1, was shown to favor specific markers and to impair dedifferentiation. This suggests that manipulation of HIF-1, could represent a promising approach to the treatment of osteoarthritis. [source]

Lowering oxygen tension enhances the differentiation of mouse embryonic stem cells into neuronal cells

BIOTECHNOLOGY PROGRESS, Issue 5 2009
Paul Mondragon-Teran
Abstract Embryonic stem cells (ESC) are capable of proliferating indefinitely in vitro whilst retaining their ability to differentiate into cells of every adult lineage. Efficient, high yield processes, which direct differentiation of ESC to specific lineages, will underpin the development of cost-effective drug screening and cell therapy products. The aim of this study was to investigate whether laboratory oxygen tension currently used for the neuronal differentiation of ESC was suboptimal resulting in inefficient process yields. An adherent monolayer protocol for the neuronal differentiation of mouse ESC (mESC) was performed in oxygen controlled chambers using a chemically defined media over an 8 day period of culture. When exposed to oxygen tensions more appropriate to in vivo neuronal development (2% O2), there was a 34-fold increase in the yield of viable cells from the differentiation process. Low oxygen tension inhibited cell death during an early phase (48 to 96 h) and toward the end (120 to 192 h) of the process. The percentage of cells expressing neuronal markers was determined by flow cytometry, revealing a small rise in the ,III tubulin and a threefold increase in the MAP2 populations at 2% O2. The total increase in the yield of viable cells expressing neuronal markers was shown to be 55-fold for ,III tubulin and 114-fold for MAP2. In conclusion, this study revealed that low oxygen tension can be used to enhance the yield of neuronal cells derived from ESCs and has implications for the development of efficient, cost-effective production processes. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source]

Activation and potentiation of the NO/cGMP pathway by NG -hydroxyl- L -arginine in rabbit corpus cavernosum under normoxic and hypoxic conditions and ageing

BRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2003
Javier Angulo
When nitric oxide synthase (NOS) produces NO from NG -hydroxy- L -arginine (OH-arginine) instead of L -arginine, the total requirement of molecular oxygen and NADPH to form NO is reduced. The aim of this work was to evaluate the effects of OH-arginine on the contractility of rabbit corpus cavernosum (RCC) and to compare the capacities of L -arginine and OH-arginine to enhance NO-mediated responses under normoxic and hypoxic conditions and in ageing, as models of defective NO production. OH-arginine, but not L -arginine, was able to relax phenylephrine-contracted rabbit trabecular smooth muscle. OH-arginine-induced relaxation was inhibited by the NOS-inhibitor, L -NNA (300 ,M), and by the guanylyl cyclase inhibitor, ODQ (20 ,M), while it was not affected by the cytochrome P450 oxygenase inhibitor, miconazole (0.1 mM). Administration of OH-arginine, but not L -arginine, produced a significant increment of cGMP accumulation in RCC tissue. Relaxation elicited by OH-arginine (300 ,M) was still observed at low oxygen tension. The increase of cGMP levels induced by ACh (30 ,M) in RCC was significantly enhanced by addition of OH-arginine (300 ,M) in normoxic conditions, as well as under hypoxia, while L -arginine did not alter the effects of ACh on cGMP accumulation. Endothelium-dependent and nitrergic nerve-mediated relaxations were both significantly reduced in RCC from aged animals (>20-months-old) when compared with young adult rabbits (5-months-old). Treatment with OH-arginine (300 ,M) significantly potentiated endothelium-dependent and neurogenic relaxation in corpus cavernosum from aged rabbits, while L -arginine (300 ,M) did not have significant effects. Results show that OH-arginine promotes NO-mediated relaxation of RCC and potentiates the NO-mediated responses induced by stimulation of endogenous NO generation in hypoxic and aged tissues. We propose that the use of OH-arginine could be of interest in the treatment of erectile dysfunction, at least in those secondary to defective NO production. British Journal of Pharmacology (2003) 138, 63,70. doi:10.1038/sj.bjp.0705027 [source]