What is oxidative metabolism

These latter studies provide direct evidence for a role of oxidative metabolism in mediating the bystander response. Active SOD and catalase enzymes were capable of suppressing these effects and also inhibited the activation in bystander cells of redox-sensitive transcription factors e.

The observation that DPI also reduced the accumulation of p53 and p21 Waf1 immunoreactive protein in bystander cells Azzam et al. NAD P H oxidase enzymes are known to produce ROS in quantities capable of stimulating signaling pathways, and these enzymes are rapidly activated by a variety of soluble mediators and engagement of cell-surface receptors Babior, While superoxide anion is the major endproduct of NAD P H-oxidase activity, hydrogen peroxide, the hydroxyl radical and hypochlorous acid are also formed as a result of its activation Halliwell and Gutteridge, ; Morel et al.

These highly reactive species can be released into the cellular environment where they can interact with closely neighboring cells or combine with serum proteins and lipids resulting in their oxidation and modulation of their function. Such activity would be consistent with a role for oxidizing diffusible factors in mediating the radiation-induced bystander response. Coupled with these observations, decreased levels of p53 and p21 Waf1 were detected. These seemingly variable results await further examination and highlight the complexity of media transfer experiments where local changes in the concentration, redox state and half-life of the diffusible factor s may take place.

Depending on their concentration, biological oxidants have been shown to both activate and inactivate signaling pathways involving tyrosine kinases, transcription factors, oxidation of key cellular thiols and calcium homeostasis Allen and Tresini, ; Gabbita et al. Furthermore, the occurrence of a conditioned medium effect that is stimulatory or toxic may be cell type, cell density and growth condition dependent. In studies utilizing other types of ionizing radiation, the antioxidant DMSO reduced the lethal effects in bystander cells produced by growing them with 3 H-thymidine-labeled cells in a three-dimensional architecture Bishayee et al.

Treatment of irradiated cultures with the antioxidants, L -lactate and L -deprenyl Mothersill et al. Nitric oxide, a small, diffusible, highly reactive molecule that is often deployed by the body as a biological signal and regulator can generate oxidative stress by decreasing glutathione levels in the cell and by forming reactive oxygen intermediates through its reaction with the superoxide radical Rubanyi et al.

Experiments showed that nitric oxide mediated the accumulation of p53 and hsp72 protein levels in wild-type p53 glioblastoma cells cocultured with, or recipient of conditioned medium from, X-irradiated mutant p53 glioblastoma cells Matsumoto et al. The accumulation of these proteins was abolished when an inhibitor of nitric oxide synthase NOS or scavengers of nitric oxide were added to the medium. In vivo experiments have also shown that inflammatory-type responses occur after exposure to ionizing radiation Lorimore et al.

In these experiments, activation of macrophages and neutrophil infiltration were not direct effects of irradiation, but were a consequence of the recognition and clearance of radiation-induced apoptotic cells. The occurrence of such a response has been suggested to provide a likely mechanism for the interactions between irradiated and nonirradiated hemopoietic cells both in vitro and in vivo Lorimore et al. Such interaction was also observed in out of field in vivo experiments examining the genetic effects of partial organ irradiation.

In related studies, in vitro clastogenic activity derived from the plasma of irradiated individuals Hollowell and Littlefield, was also inhibited by SOD Emerit et al. Oxidative-stress mediators have also been implicated in abscopal effects, whereby cytotoxic effects are observed in solid tumors located at distant sites from those targeted by radiation.

It is thought that such effects are mediated by redox-sensitive cytokines that are cytotoxic Ohba et al. Furthermore, genomic instability in the progeny of cells surviving a radiation exposure has been associated with intracellular oxidants, oxidative DNA base damage and vulnerability to free radical membrane damage Clutton et al.

Overall, the above studies challenge the traditional paradigm that the important biological effects of ionizing radiation are a result of DNA damage by its direct interaction with the nucleus. They indicate that irradiated and nonirradiated cells interact, and oxidative metabolism has an essential role in the signaling events leading to radiation-induced bystander effects.

Preliminary evidence indicates that oxidants modulate similar signal transduction pathways in irradiated and bystander cells and contribute to the induction of bystander DNA damage. Genes that are directly responsive to oxidative stress have been identified in bystander cells Azzam et al. However, direct evidence explaining how these events occur is still lacking.

Do the characterized signaling events lead to DNA damage in bystander cells or are they a result of its occurrence? Do oxidants positively regulate specific pathways while negatively regulating others? Are signaling molecules other than MAPK and p53 e. Such studies would further help identify soluble bystander mediators and enhance our understanding of the underlying mechanisms.

While it has been argued that oxidants mediate the induction of DNA damage in bystander cells, it is unclear how the required concentrations of such oxidants are achieved. Are oxidants strictly of cytoplasmic and membrane origin or is the mitochondria also a main source? Cytotoxic aldehydes produced as a result of cell membrane lipid peroxidation have been cited as mediators of the bystander effect, yet such oxidant-induced lipid modifications have not been characterized.

Interestingly, superoxide is known to permeate lipid membranes and in the presence of oxygen leads to the formation of hydroperoxide and the pentadienyl radical. The latter can trigger further reactions leading to elaboration of more superoxide and propagation of lipid peroxidation Petkau, ; Chuaqui and Petkau, that may contribute to persistent propagation of bystander effects.

Expansion of these various studies and the use of genetic approaches where the expression levels of oxidant generators or scavengers are modulated in irradiated or bystander cells should enhance our understanding of the role of oxidative metabolism. Often, chemical inhibitors of oxidants or probes to detect them lack specificity Burkitt and Wardman, and the ability of some antioxidants to permeate into cells has been questioned; genetic approaches would alleviate these difficulties.

Homeostatic maintenance of cells in tissues depends on a complex network of communication modalities that allow coordinated interactions among themselves and with their environment. Cells respond to factors in the extracellular matrix and they are linked to each other by specialized cell junctions. Occluding, anchoring and communicating type junctions that synchronize the activities of cells in multicellular tissues have been described.

Among these, the gap junction is one of the most widespread, being found in most animal tissues and perhaps all animal species. It is a specialized plasma membrane structure, which contains a low resistance channel linking adjacent cells. In excitable tissues, it permits electrical coupling; in others, it allows passage of small molecules involved in metabolic support, growth control and embryogenesis Kumar and Gilula, ; Lo, ; Simon and Goodenough, A gap junction consists of a complete cell-to-cell channel that spans two plasma membranes and results from the association of two half channels, or connexons, contributed separately by each of the two participating cells.

Each connexon, in turn, is a multimeric assembly of protein subunits called connexins Bruzzone et al. Connexins are an extensive family of proteins comprising several members Willecke et al.

Different connexins are expressed in different tissues and have different selectivity related to the size and charge of the communicated molecules Veenstra, Studies have revealed that channels composed of different connexins have different conductances and permeability to ions and specific fluorescent dyes, and that the rate of permeation is dependent on the connexin composition of the gap-junction channel Elfgang et al.

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Ley, M. Mahowald, V. Magrini, E. Mardis, and J. Ridaura, J. Faith, F. Rey et al. Bolca, T. In this tutorial, you will also know the common metabolic pathways of biomolecules, such as glucose and other carbohydrates, fats, proteins and amino acids, and essential nutrients Plants are responsible for incredible feats of molecular transformation.

Plant processes, such as photosynthesis, photophosphorylation, chemiosmosis, carbon fixing reactions, respiration, are presented in this tutorial A chemical process in which oxygen is used to make energy from carbohydrates sugars. Also called aerobic metabolism , aerobic respiration , and cell respiration. NCI Dictionary. Sign In.