Cellular redox state

If cellular redox state, determined by the glutathione status of the heart, plays a role in the modulation of ion transporter activity in cardiac tissue, it is important to identify possible mechanisms by which these effects are mediated. Protein S-,thiolation is a process that was originally used to describe the formation of adducts of proteins with low molecular thiols such as glutathione (Miller etal., 1990). In view of the significant alterations of cardiac glutathione status (GSH and GSSG) and ion-transporter activity during oxidant stress, the process of S-thiolation may be responsible for modifications of protein structure and function. 

Westendorp MO, Shatrov VA, Schulze-Osthoff K, Frank R, Kraft M, Los M, Krammer PH, Droge W, Lehmann V (1995) HlV-1 Tat potentiates TNF-induced NF-kappa B activation and cytotoxicity by altering the cellular redox state. Embo J 14 546—554... 

McCullough KD, Martindale JL, Klotz LO, Aw TY, Holbrook NJ (2001), Gaddi 53 sensitizes cells to endoplasmic reticulum stress by downregulating Bcl-2 and perturbing the cellular redox state, Mol. Cell Biol. 21 1249-1259. 

Mukherjee SP, Lynn WS. 1979. Role of cellular redox state and glutathione in adenylate cyclase activity in rat adipocytes. Biochim Biophys Acta 568 224-233. 

Lopez-Lluch G, Blazquez MV, Perez-Vicente R, Macho A, Buron Ml, Alcain EJ, Munoz E, and Navas P (2001) Cellular redox state and activating protein-1 are involved in ascorbate effect on calcitriol-induced differentiation. Protoplasma 217,129-36. 

The fungal metabolite scyphostatin (Fig. 7) is a potent, reversible inhibitor of membrane-bound Mg +-dependent neutral sphingomyelinase (nSMase), thereby interfering with the generation of ceramide (102, 103). The activity of nSMases is sensitive to the cellular redox state, for example, the ratio of glutathione in the reduced versus the oxidized form (104, 105). The famesyltransferase inhibitor manumycin A, a polyenamide produced by the Streptomyces species, also inhibits nSMase irreversibly (106). 

Temporal patterns and oscillations have been observed in a very broad spectrum across various spatial scales. For example, periodic dynamics have been studied in gene expression patterns in the cell division cycle and the cellular redox state alterations, while the genome-wide oscillations at the transcript and protein levels indicate the cell cycle as a developmental process [33]. Spatiotemporal oscillations have been observed in mitochondria, transmembrane potentials, heart excitation waves, neural activities and brain dynamics, cognition and verbal working memory, and even bacteria [16, 34-37]. 

Glutathione (GSH) is one of the most important intracellular antioxidant molecules which serve to protect against ROS, as well as for detoxification of xenobiotics, removal of hydroperoxides, and maintenance of the cellular redox state. However, large quantities of ROS or reactive metabolites may lead to reduction/deple-tion of intracellular GSH level which will have deleterious consequences for the cell. GSH may be measured by monochlorbi-mane (mBCl), a lipophilic probe that passively diffuses across... 

While the primary physiological role of MT involves the homeostasis of zinc and copper, it remains that MT also has a role in the cellular defense against cadmium and mercury. In addition, being a thiol containing protein MT has the potential to be an effective free radical scavenger, therefore, important in regulating the cellular redox-state. 

The change in the intensity of the blue-shifted BL of P. phosphoreum (Fig. 3) may be ascribed to the change in apportionment of the respiratory reducing power to the luciferases reaction. Furthermore, it seems that the highly fluorescent property of lumazine protein is hardly influenced by the redox state of the respiratory components unlike YFP. That is, the cellular redox state may not be influential in the electronic excitation transfer interaction responsible for the blue-shifted BL. 

We have now accrued considerable evidence that reversed electron transfer provides the driving force that poises the redox couples of living cells and enables reductive syntheses.This work is still in progress, but already an understanding of the mechanisms by which energy flow drives proton current to poise both the phosphorylation state (by control of ATP synthesis) and the various cellular redox states (by control of reversed electron transfer) seems closer. 

Fig. 2. Interplay among superoxide anion, nitric oxide, and eicosanoids in high oxidative stress. The biological function of nitric oxide in target cells is influenced by the cellular redox state. In increased oxidative stress, which results in an oxidizing environment, NO readily form free radicals, including the highly reactive peroxynitrite (OONO ). Peroxynitrite can influence eicosanoid synthesis by interfering with different enzyme systems of the arachidonic acid cascade. Increased free radicals may also catalyze nonenzymic peroxidation of membrane PUFA (e.g., arachidonic acid), resulting in increased production of isoprostanes that possess potent vasoconstrictor activity. PLA, phospholipase NO, nitric oxide NOS, nitric oxide synthase NADPH oxidase, vascular NAD(P)H oxidase 02 , superoxide anion PUFA, polyunsaturated fatty acids EPA, eicosapentaenoic acid DHA, docosahexaenoic acid COX, cyclooxygenase PGI2 synthase, prostacyclin synthase.

A shift in the cellular reduction/oxidation (redox) state has been found to be involved in the process of apoptosis. Generally, the cellular redox state is a balance between the relative quantities of the intracellular oxidative substances (reactive oxygen species, ROS) and reductive substances (reduced glutathione, GSH). A microfluidic device method with laser-induced fluorescence (LIF) detection for simultaneous, rapid determination of intracellular ROS and GSH in apoptotic leukemia cells has been described. 

Alcohol also increases the exhalation of metallic mercury in mice previously treated with mercuric chloride (Magos et al., 1973 Dunn et al., 1981). These findings can be explained by an inhibition of the peroxidase reaction of catalase in that the alcohol is oxidised instead of the mercury. Aminotriazol, a well known inhibitor of catalase, has the same effect (Magos et al., 1974) (Fig. 1). Tocopherol, which also affects the cellular redox state, reduces the toxicity of mercury as well (Welsh and Soares, 1973). 

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