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      Taurine protection of PC12 cells against endoplasmic reticulum stress induced by oxidative stress

      review-article
      1 , 2 , 2 , , 2 ,
      Journal of Biomedical Science
      BioMed Central
      17th International Meeting of Taurine
      14–19 December 2009

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          Abstract

          Background

          Taurine is a free amino acid present in high concentrations in a variety of organs of mammalians. As an antioxidant, taurine has been found to protect cells against oxidative stress, but the underlying mechanism is still unclear.

          Methods

          In this report, we present evidence to support the conclusion that taurine exerts a protective function against endoplasmic reticulum (ER) stress induced by H 2O 2 in PC 12 cells. Oxidative stress was introduced by exposure of PC 12 cells to 250 uM H 2O 2 for 4 hours.

          Results

          It was found that the cell viability of PC 12 cells decreased with an increase of H 2O 2 concentration ranging from approximately 76% cell viability at 100 uM H 2O 2 down to 18% at 500 uM H 2O 2. At 250 uM H 2O 2, cell viability was restored to 80% by taurine at 25 mM. Furthermore, H 2O 2 treatment also caused a marked reduction in the expression of Bcl-2 while no significant change of Bax was observed. Treatment with taurine restored the reduced expression of Bcl-2 close to the control level without any obvious effect on Bax. Furthermore, taurine was also found to suppress up-regulation of GRP78, GADD153/CHOP and Bim induced by H 2O 2, suggesting that taurine may also exert a protective function against oxidative stress by reducing the ER stress.

          Conclusion

          In summary, taurine was shown to protect PC12 cells against oxidative stress induced by H 2O 2. ER stress was induced by oxidative stress and can be suppressed by taurine.

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          Most cited references31

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          Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death.

          Bcl-2 protein is able to repress a number of apoptotic death programs. To investigate the mechanism of Bcl-2's effect, we examined whether Bcl-2 interacted with other proteins. We identified an associated 21 kd protein partner, Bax, that has extensive amino acid homology with Bcl-2, focused within highly conserved domains I and II. Bax is encoded by six exons and demonstrates a complex pattern of alternative RNA splicing that predicts a 21 kd membrane (alpha) and two forms of cytosolic protein (beta and gamma). Bax homodimerizes and forms heterodimers with Bcl-2 in vivo. Overexpressed Bax accelerates apoptotic death induced by cytokine deprivation in an IL-3-dependent cell line. Overexpressed Bax also counters the death repressor activity of Bcl-2. These data suggest a model in which the ratio of Bcl-2 to Bax determines survival or death following an apoptotic stimulus.
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            Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death.

            To extend the mammalian cell death pathway, we screened for further Bcl-2 interacting proteins. Both yeast two-hybrid screening and lambda expression cloning identified a novel interacting protein, Bad, whose homology to Bcl-2 is limited to the BH1 and BH2 domains. Bad selectively dimerized with Bcl-xL as well as Bcl-2, but not with Bax, Bcl-xs, Mcl-1, A1, or itself. Bad binds more strongly to Bcl-xL than Bcl-2 in mammalian cells, and it reversed the death repressor activity of Bcl-xL, but not that of Bcl-2. When Bad dimerized with Bcl-xL, Bax was displaced and apoptosis was restored. When approximately half of Bax was heterodimerized, death was inhibited. The susceptibility of a cell to a death signal is determined by these competing dimerizations in which levels of Bad influence the effectiveness of Bcl-2 versus Bcl-xL in repressing death.
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              Oxidation of biological systems: oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification.

              Reactive oxygen species (ROS) and other radicals are involved in a variety of biological phenomena, such as mutation, carcinogenesis, degenerative and other diseases, inflammation, aging, and development. ROS are well recognized for playing a dual role as deleterious and beneficial species. The objectives of this review are to describe oxidative stress phenomena, terminology, definitions, and basic chemical characteristics of the species involved; examine the biological targets susceptible to oxidation and the defense mechanisms of the organism against these reactive metabolites; and analyze methodologies, including immunohistochemical markers, used in toxicological pathology in the visualization of oxidative stress phenomena. Direct detection of ROS and other free radicals is difficult, because these molecules are short-lived and highly reactive in a nonspecific manner. Ongoing oxidative damage is, thus, generally analyzed by measurement of secondary products including derivatives of amino acids, nuclei acids, and lipid peroxidation. Attention has been focused on electrochemical methods based on voltammetry measurements for evaluating the total reducing power of biological fluids and tissues. This approach can function as a tool to assess the antioxidant-reducing profile of a biological site and follow changes in pathological situations. This review thus includes different topics essential for understanding oxidative stress phenomena and provides tools for those intending to conduct study and research in this field.
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                Author and article information

                Conference
                J Biomed Sci
                Journal of Biomedical Science
                BioMed Central
                1021-7770
                1423-0127
                2010
                24 August 2010
                : 17
                : Suppl 1
                : S17
                Affiliations
                [1 ]Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL 33431, USA
                [2 ]Department of Biomedical Science, Florida Atlantic University, Boca Raton, FL 33431, USA
                Article
                1423-0127-17-S1-S17
                10.1186/1423-0127-17-S1-S17
                2994405
                20804591
                859e4272-46fa-4a8b-8bf5-cdef5dc83986
                Copyright ©2010 Prentice and Wu; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                17th International Meeting of Taurine
                Fort Lauderdale, FL, USA
                14–19 December 2009
                History
                Categories
                Review

                Molecular medicine
                Molecular medicine

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