scholarly journals The Membrane Electrical Potential and Intracellular pH as Factors Influencing Intracellular Ascorbate Concentration and Their Role in Cancer Treatment

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2964
Author(s):  
Mateusz Gąbka ◽  
Paulina Dałek ◽  
Magdalena Przybyło ◽  
Daniel Gackowski ◽  
Ryszard Oliński ◽  
...  

Ascorbate is an important element of a variety of cellular processes including the control of reactive oxygen species levels. Since reactive oxygen species are implicated as a key factor in tumorigenesis and antitumor therapy, the injection of a large amount of ascorbate is considered beneficial in cancer therapy. Recent studies have shown that ascorbate can cross the plasma membrane through passive diffusion. In contrast to absorption by active transport, which is facilitated by transport proteins (SVCT1 and SVCT2). The passive diffusion of a weak acid across membranes depends on the electrostatic potential and the pH gradients. This has been used to construct a new theoretical model capable of providing steady-state ascorbate concentration in the intracellular space and evaluating the time needed to reach it. The main conclusion of the analysis is that the steady-state intracellular ascorbate concentration weakly depends on its serum concentration but requires days of exposure to saturate. Based on these findings, it can be hypothesized that extended oral ascorbate delivery is possibly more effective than a short intravenous infusion of high ascorbate quantities.

Surgery ◽  
2015 ◽  
Vol 158 (3) ◽  
pp. 827-836 ◽  
Author(s):  
Yueming Zhu ◽  
Pritha Paul ◽  
Sora Lee ◽  
Brian T. Craig ◽  
Eric J. Rellinger ◽  
...  

Nanoscale ◽  
2018 ◽  
Vol 10 (34) ◽  
pp. 15911-15917 ◽  
Author(s):  
Erik Jacques ◽  
Manuel Ahumada ◽  
Brianna Rector ◽  
Goonay Yousefalizadeh ◽  
Constanza Galaz-Araya ◽  
...  

Free radical oxidation of CLP-Trp peptides@AgNPs was studied using steady state & ultrafast spectroscopy and molecular dynamics.


Author(s):  
Valentina R. Haritonova ◽  
Alexander V. Sidorov

A fluorescent dye 2′,7′-dichlorodihydrofluorescein diacetate was used to characterize an accumulation of reactive oxygen species (ROS) in the primary culture (72 and 144 h) of neurons of the central ganglia of the mollusc Lymnaea stagnalis under conditions of acute, induced oxidative stress. It was found that larger cells accumulate a greater amount of ROS. High values of the relative (per unit area) fluorescence, indicating an increase in the amount of ROS per unit of intracellular space, are characteristic of smaller neurons of 72-hour culture. Changes in relative fluorescence over time are different from each other in neurons of 72- and 144-hour cultures. For an older culture, a negative, statistically significant relationship was noted (R = – 0.31), and for cells of 72 h of cultivation, a statistically significant correlation was not found (R = 0.12). It is assumed that the discovered relationship between the size (shape) of a neuron and its ability to resist the accumulation of ROS in the cytosol indicates differences in the resistance of CNS neurons to oxidative damage depending on their place and position in the neural network, thereby ensuring the selective stability of neuronal functions under conditions of oxidative stress.


2007 ◽  
Vol 292 (1) ◽  
pp. H101-H108 ◽  
Author(s):  
David L. Hoffman ◽  
Jason D. Salter ◽  
Paul S. Brookes

Mitochondria are proposed to play an important role in hypoxic cell signaling. One currently accepted signaling paradigm is that the mitochondrial generation of reactive oxygen species (ROS) increases in hypoxia. This is paradoxical, because oxygen is a substrate for ROS generation. Although the response of isolated mitochondrial ROS generation to [O2] has been examined previously, such investigations did not apply rigorous control over [O2] within the hypoxic signaling range. With the use of open-flow respirometry and fluorimetry, the current study determined the response of isolated rat liver mitochondrial ROS generation to defined steady-state [O2] as low as 0.1 μM. In mitochondria respiring under state 4 (quiescent) or state 3 (ATP turnover) conditions, decreased ROS generation was always observed at low [O2]. It is concluded that the biochemical mechanism to facilitate increased ROS generation in response to hypoxia in cells is not intrinsic to the mitochondrial respiratory chain alone but may involve other factors. The implications for hypoxic cell signaling are discussed.


2012 ◽  
Vol 29 (6) ◽  
pp. 555-566 ◽  
Author(s):  
María Mirian Estévez-Carmona ◽  
Estela Meléndez-Camargo ◽  
Rocio Ortiz-Butron ◽  
Marisol Pineda-Reynoso ◽  
Margarita Franco-Colin ◽  
...  

2009 ◽  
pp. c3 ◽  
Author(s):  
Helena M. Cochemé ◽  
Michael P. Murphy

2004 ◽  
Vol 71 ◽  
pp. 121-133 ◽  
Author(s):  
Ascan Warnholtz ◽  
Maria Wendt ◽  
Michael August ◽  
Thomas Münzel

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.


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