Anoxia-Induced Changes in Pyridine Nucleotide Redox State in Cortical Neurons and Astrocytes

Kahraman, Sibel; Fiskum, Gary

doi:10.1007/s11064-006-9206-8

Cited by 13 publications

(11 citation statements)

References 30 publications

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“…These results are consistent with our results previously obtained in tumor cells (31), and conform with the classical view of decreased metabolic flux through the OPPC under hypoxia (30, 32, 33), whereby removal of O 2 leads to a reducing environment. For example, Scholz et al measured an increase in NADPH fluorescence in rat liver within seconds of exposure to near anoxic pO 2 , and measured a new steady state within minutes (30).…”

Section: Discussionsupporting

confidence: 93%

pO2-dependent NO production determines OPPC activity in macrophages

Robinson

Tuttle

Otto

et al. 2010

Free Radical Biology and Medicine

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Stimulated macrophages produce nitric oxide (NO) via inducible nitric oxide synthase (iNOS) using molecular O2, L-arginine, and NADPH. Exposure of macrophages to hypoxia decreases NO production within seconds suggesting substrate limitation as the mechanism. Conflicting data exist regarding the effect of pO2 on NADPH production via the oxidative pentose phosphate cycle (OPPC). Therefore, the present studies were developed to determine whether NADPH could be limiting for NO production under hypoxia. Production of NO metabolites (NOx) and OPPC activity by RAW 264.7 cells was significantly increased by stimulation with lipopolysaccharide (LPS) and interferon γ (IFNγ) at pO2 ranging from 0.07% to 50%. OPPC activity correlated linearly with NOx production at pO2 > 0.13%. Increased OPPC activity by stimulated RAW 264.7 cells was significantly reduced by 1400W, an iNOS inhibitor. OPPC activity was significantly increased by concomitant treatment of stimulated RAW 264.7 cells with chemical oxidants such as hydroxy-ethyldisulfide or pimonidazole, at 0.07% and 50% O2, without decreasing NOx production. These results are the first to investigate the effect of pO2 on the relationship between NO production and OPPC activity, and to rule out limitations in OPPC activity as a mechanism by which NO production is decreased under hypoxia.

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Section: Discussionsupporting

confidence: 93%

pO2-dependent NO production determines OPPC activity in macrophages

Robinson

Tuttle

Otto

et al. 2010

Free Radical Biology and Medicine

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“…Therefore, we investigated the effect of respiratory inhibitors upon NAD(P)H fluorescence. We reasoned that if the NAD(P)H signal represented mitochondrial reductant, we would see an increase in fluorescence upon treatment with inhibitor (Fisher et al, 1976;Kahraman and Fiskum, 2007). We tried all three inhibitors and found similar results with each; to remain concise, we will present the results only from oligomycin (Supplemental Fig.…”

Section: The Nad(p)h Signal Reflects Mitochondrial Nad(p)h Utilizationmentioning

confidence: 97%

Oscillatory Growth in Lily Pollen Tubes Does Not Require Aerobic Energy Metabolism

et al. 2009

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Oscillatory tip growth in pollen tubes depends on prodigious amounts of energy. We have tested the hypothesis that oscillations in the electron transport chain lead to growth oscillations in lily (Lilium formosanum). Using three respiratory inhibitors, oligomycin, antimycin A, and cyanide, we find that pollen tube growth is much less sensitive to respiratory inhibition than respiration is. All three block respiration at concentrations severalfold lower than necessary to inhibit growth. Mitochondrial NAD(P)H and potentiometric JC-1 fluorescence, employed as markers for electron transport chain activity, rise rapidly in response to oligomycin, as expected. Pollen tube growth stops for several minutes before resuming. Subsequent growth has a lower mean rate, but continues to oscillate, albeit with a longer period. NAD(P)H fluorescence no longer exhibits coherent oscillations, and mitochondria no longer congregate directly behind the apex: they distribute evenly throughout the cell. Postinhibition growth relies on aerobic fermentation for energy production as revealed by an increase in ethanol in the media. These data suggest that oscillatory growth depends not on a single oscillatory pacemaker but rather is an emergent property arising from a number of stable limit cycles.

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“…These considerations have led a number of groups to refer to “NAD(P)H” auofluorecence, to acknowledge the possible contribution from both reduced pyridine nucleotides (e.g. Duchen, 1992; Barbour et al, 1993; Patterson et al, 2000; Schuchmann et al, 2001; Huang et al, 2002; Kunz et al, 2002; Kann et al, 2003; Shuttleworth et al, 2003; Galeffi et al, 2007; Kahraman and Fiskum, 2007) and this terminology will be used in the following discussion of responses to nerve stimulation.…”

Section: Nadph and Nad(p)h Autofluorescencementioning

confidence: 99%

Use of NAD(P)H and flavoprotein autofluorescence transients to probe neuron and astrocyte responses to synaptic activation

Shuttleworth

2010

Neurochemistry International

105

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Synaptic stimulation in brain slices is accompanied by changes in tissue autofluorescence, which are a consequence of changes in tissue metabolism. Autofluorescence excited by ultraviolet light has been most extensively studied, and is due to reduced pyridine nucleotides (NADH and NADPH, collectively termed NAD(P)H). Stimulation generates a characteristic compound NAD(P)H response, comprising an initial fluorescence decrease and then an overshooting increase that slowly recovers to baseline levels. Evoked NAD(P)H transients are relatively easy to record, do not require the addition of exogenous indicators and have good signal-noise ratios. These characteristics make NAD(P)H imaging methods very useful for tracking the spread of neuronal activity in complex brain tissues, however the cellular basis of synaptically-evoked autofluorescence transients has been the subject of recent debate. Of particular importance is the question of whether signals are due primarily to changes in neuronal mitochondrial function, and/or whether astrocyte metabolism triggered by glutamate uptake may be a significant contributor to the overshooting NAD(P)H fluorescence increases. This mini-review addresses the subcellular origins of NAD(P)H autofluorescence and the evidence for mitochondrial and glycolytic contributions to compound transients. It is concluded that there is no direct evidence for a contribution to NAD(P)H signals from glycolysis in astrocytes following synaptic glutamate uptake. In contrast, multiple lines of evidence, including from complimentary flavoprotein autofluorescence signals, imply that mitochondrial NADH dynamics in neurons dominate compound evoked NAD(P)H transients. These signals are thus appropriate for studies of mitochondrial function and dysfunction in brain slices, in addition to providing robust maps of postsynaptic neuronal activation following physiological activation.

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Anoxia-Induced Changes in Pyridine Nucleotide Redox State in Cortical Neurons and Astrocytes

Cited by 13 publications

References 30 publications

pO2-dependent NO production determines OPPC activity in macrophages

pO2-dependent NO production determines OPPC activity in macrophages

Oscillatory Growth in Lily Pollen Tubes Does Not Require Aerobic Energy Metabolism

Use of NAD(P)H and flavoprotein autofluorescence transients to probe neuron and astrocyte responses to synaptic activation

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