scholarly journals NADH/NAD redox state of cytoplasmic glycolytic compartments in vascular smooth muscle

2000 ◽  
Vol 279 (6) ◽  
pp. H2872-H2878 ◽  
Author(s):  
John T. Barron ◽  
Liping Gu ◽  
Joseph E. Parrillo

The cytoplasmic NADH/NAD redox potential affects energy metabolism and contractile reactivity of vascular smooth muscle. NADH/NAD redox state in the cytosol is predominately determined by glycolysis, which in smooth muscle is separated into two functionally independent cytoplasmic compartments, one of which fuels the activity of Na+-K+-ATPase. We examined the effect of varying the glycolytic compartments on cystosolic NADH/NAD redox state. Inhibition of Na+-K+-ATPase by 10 μM ouabain resulted in decreased glycolysis and lactate production. Despite this, intracellular concentrations of the glycolytic metabolite redox couples of lactate/pyruvate and glycerol-3-phosphate/dihydroxyacetone phosphate (thus NADH/NAD) and the cytoplasmic redox state were unchanged. The constant concentration of the metabolite redox couples and redox potential was attributed to 1) decreased efflux of lactate and pyruvate due to decreased activity of monocarboxylate B-H+ transporter secondary to decreased availability of H+ for cotransport and 2) increased uptake of lactate (and perhaps pyruvate) from the extracellular space, probably mediated by the monocarboxylate-H+ transporter, which was specifically linked to reduced activity of Na+-K+-ATPase. We concluded that redox potentials of the two glycolytic compartments of the cytosol maintain equilibrium and that the cytoplasmic NADH/NAD redox potential remains constant in the steady state despite varying glycolytic flux in the cytosolic compartment for Na+-K+-ATPase.

1998 ◽  
Vol 274 (1) ◽  
pp. C88-C96 ◽  
Author(s):  
Christopher D. Hardin ◽  
Dorian R. Finder

To determine whether channeling of glycolytic intermediates can occur in vascular smooth muscle (VSM), we permeabilized freshly isolated VSM cells from hog carotid arteries with dextran sulfate. The dextran sulfate-treated cells did not exclude trypan blue, a dye with molecular weight of ∼1,000. If glycolytic intermediates freely diffuse, plasmalemmal permeabilization would allow intermediates to exit the cell and glycolytic flux should cease. We incubated permeabilized and nonpermeabilized cells with 5 mM [1-13C]glucose at 37°C for 3 h. 13C nuclear magnetic resonance (NMR) was used to determine relative [3-13C]lactate production and to identify any13C-labeled glycolytic intermediates that exited from the permeabilized cells. [3-13C]lactate production from [1-13C]glucose was decreased by an average of 32% ( n = 6) in permeabilized cells compared with intact cells. No13C-labeled glycolytic intermediates were observed in the bathing solution of permeabilized cells. We conclude that channeling of glycolytic intermediates can occur in VSM cells.


1994 ◽  
Vol 267 (2) ◽  
pp. H764-H769 ◽  
Author(s):  
J. T. Barron ◽  
S. J. Kopp ◽  
J. Tow ◽  
J. E. Parrillo

The influence of octanoate on O2 consumption, tricarboxylic acid (TCA) cycle intermediates, and high-energy phosphates was examined in intact resting porcine carotid artery to investigate the role of fatty acid in energy metabolism and its integration with glucose metabolism in vascular smooth muscle. Incubation of resting arteries with octanoate (0.5 mM), which was previously shown to inhibit aerobic glycolysis (6), inhibited lactate production by 64% and increased O2 consumption by 30%. The increase in O2 consumption with octanoate was approximately equal to that calculated to account for the ATP production lost by inhibition of aerobic lactate production by octanoate. In glucose-free medium, the level of high-energy phosphate was reduced but was restored when octanoate was included in the incubation medium. This was associated with an increase in O2 consumption. These results suggest that the energy requirements of resting carotid artery can be largely met by the oxidative metabolism of fatty acid. Octanoate induced anaplerosis of the TCA cycle, as indicated by a 70% increase in the level of citrate. Extracellular glucose was necessary for octanoate-induced anaplerosis, probably by providing the extra carbon via pyruvate carboxylation, whereas a coupled transamination involving aspartate was a less important anaplerotic mechanism.


1984 ◽  
Vol 39 (11-12) ◽  
pp. 1141-1144 ◽  
Author(s):  
Helmut Heinle ◽  
Gerhard Sigg ◽  
Amo Reich ◽  
Klaus-Ulrich Thiedemann

Abstract Vascular smooth muscle cells from rabbit arteries were grown in tissue culture and stimulated by DC impulses (1 mA, 1V, 10 Hz, 1 ms/imp). Scanning microscopic examination disclosed that in stimulated cultures the cell surface was enlarged by numerous microvilli. This was interpreted as being indicative of an increase in cell activity. Cellular metabolism was character­ized by analyzing the incubation medium for glucose, glutamate/glutamine, and lactate. When compared to unstimulated controls, stimulation caused an increase in the uptake of glucose and glutamine as well as an increased lactate production. The enhancing effect on metabolism was prevented when the “calcium antagonist” verapamil was present (5 × 10-6ᴍ). Although the exact mechanism by which DC stimulation influences the cells remains obscure, this finding indicates an important mediating role of Ca2+ ions.


2016 ◽  
Vol 311 (4) ◽  
pp. H944-H957 ◽  
Author(s):  
Jason Boehme ◽  
Xutong Sun ◽  
Kathryn V. Tormos ◽  
Wenhui Gong ◽  
Manuela Kellner ◽  
...  

Vascular cell hyperproliferation and metabolic reprogramming contribute to the pathophysiology of pulmonary arterial hypertension (PAH). An important cause of PAH in children with congenital heart disease (CHD) is increased pulmonary blood flow (PBF). To better characterize this disease course we studied early changes in pulmonary artery smooth muscle cell (PASMC) proliferation and metabolism using a unique ovine model of pulmonary overcirculation. Consistent with PAH in adults, PASMCs derived from 4-wk-old lambs exposed to increased PBF (shunt) exhibited increased rates of proliferation. While shunt PASMCs also exhibited significant decreases in mitochondrial oxygen consumption, membrane potential, and tricarboxylic acid (TCA) cycle function, suggesting a switch to Warburg metabolism as observed in advanced PAH in adults, they unexpectedly demonstrated decreased glycolytic lactate production, likely due to enhanced flux through the pentose phosphate pathway (PPP). This may be a response to the marked increase in NADPH oxidase (Nox) activity and decreased NADPH/NADP+ ratios observed in shunt PASMCs. Consistent with these findings, pharmacological inhibition of Nox activity preferentially slowed the growth of shunt PASMCs in vitro. Our results therefore indicate that PASMC hyperproliferation is observed early in the setting of pulmonary overcirculation and is accompanied by a unique metabolic profile that is independent of HIF-1α, PDHK1, or increased glycolytic flux. Our results also suggest that Nox inhibition may help prevent pulmonary overcirculation-induced PAH in children born with CHD.


1980 ◽  
Vol 187 (2) ◽  
pp. 367-370 ◽  
Author(s):  
L Morpurgo ◽  
M T Graziani ◽  
A Desideri ◽  
G Rotilio

1. Redox titrations are reported of the metal centres in Japanese-lacquer-tree (Rhus vernicifera) laccase with ferrocyanide. 2. The redox potential of Type 1 Cu was found to increase with ferrocyanide concentration up to a limiting value similar to that for the Type 1 Cu in Type 2 Cu-depleted enzyme (which is independent of ferrocyanide concentration). 3. The redox potential of the two-electron acceptor (Type 3 Cu) is also independent of ferrocyanide concentration in Type 2 Cu-depleted enzyme and lower than values reported for the native enzyme. 4. The two-electron acceptor is present in the oxidized state in the Type 2 Cu-depleted enzyme, though the latter lacks the 330 nm absorption band. 5. The redox potential of Type 2 Cu also depends on ferrocyanide concentration, at least in the presence of azide. 6. The redox potentials are affected by freezing the solutions and/or addition of azide, the latter binding to Type 2 Cu with affinity dependent on the redox state of the two-electron acceptor.


FEBS Letters ◽  
2008 ◽  
Vol 582 (5) ◽  
pp. 635-642 ◽  
Author(s):  
Walter Malorni ◽  
Elisabetta Straface ◽  
Paola Matarrese ◽  
Barbara Ascione ◽  
Rita Coinu ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3557
Author(s):  
Rosa Edith Grijalva-Guiza ◽  
Aura Matilde Jiménez-Garduño ◽  
Luis Ricardo Hernández

Flavonoids are a group of secondary metabolites derived from plant-based foods, and they offer many health benefits in different stages of several diseases. This review will focus on their effects on ion channels expressed in vascular smooth muscle during atherosclerosis. Since ion channels can be regulated by redox potential, it is expected that during the onset of oxidative stress-related diseases, ion channels present changes in their conductive activity, impacting the progression of the disease. A typical oxidative stress-related condition is atherosclerosis, which involves the dysfunction of vascular smooth muscle. We aim to present the state of the art on how redox potential affects vascular smooth muscle ion channel function and summarize if the benefits observed in this disease by using flavonoids involve restoring the ion channel activity.


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