1,721,179 research outputs found
Cell signalling and the glutathione redox system
No full textThe reduction/oxidation (redox) state of the cell is a consequence of the balance between the levels of oxidising and reducing equivalents. A reducing intracellular environment is often associated with cell survival; however, redox unbalance is necessary since it represents a regulatory sensor for several nuclear transcription factors. Activator protein 1 (AP-1), nuclear factor-κB (NF-κB) and protein tyrosine phosphatases 1-B (PTP-1B) are some of the well-known molecular factors for which a redox modulation of their activity has been demonstrated. The glutathione buffer system modulates cell response to redox changes induced by either external or intracellular stimuli. This paper summarises recent knowledge on the role played by several redox modulators in inducing signalling events that finally regulate cell cycle progression. © 2002 Elsevier Science Inc. All rights reserved
Effect of the redox state of the red blood cell components on the inactivation of glutathione peroxidase by divicine
No full textThe redox state of red blood cell components was found to have profound effects on the specific inactivation of erythrocyte glutathione (GSH) peroxidase by divicine, a hydroquinone imine molecule of fava beans likely to be responsible, through redox cycling, of the oxidative damage of red blood cells ultimately resulting in the hemolysis of favism. Oxidation of hemoglobin is a necessary step for the inactivation to take place, apparently as a H2O2-MetHb adduct. On the other hand, the presence of either reduced NADP or glutathione enhances the inactivating effect although NADPH inhibits the oxidation of hemoglobin, and this suggests a catalytic role for MetHb in the inactivation process
Inactivation of red cell glutathione peroxidase by divicine and its relation to the hemolysis of favism
No full textA significant inactivation of red blood cell glutathione peroxidase (25% less than the physiological value) was observed after exposure of intact erythrocytes to 2 mM divicine (an autoxidizable aminophenol from Vicia faba seeds) and 2 mM ascorbate for 3 h at 37 degrees C. Addition of catalase and conversion of Hb to the carbomonoxy derivative resulted in protection against enzyme inactivation. Oxidation of Hb was a concurrent phenomenon, and augmented the inactivating effect. In hemolysates, much stronger effects were observed at shorter times (2 h); divicine was effective also without ascorbate, and the presence of reductants (ascorbate or glutathione or NADPH) enhanced its inactivating power. Of the other antioxidant enzymes, superoxide dismutase was unaffected under the same experimental conditions. Catalase was found to be much less sensitive to the inactivation; it was almost unaffected in experiments with intact erythrocytes and specifically protected by NADPH in experiments with hemolysates. This specific damage of glutathione peroxidase, apparently involving interaction of H2O2 and HbO2, may be related to the pathogenesis of hemolysis in favism
Inattivazione della glutatione perossidasi in globuli rossi trattati con ascorbato e vicina
No full textMultiple electrophoretic variants of Cu, Zn superoxide dismutase as expression of the enzyme aging. Effects of H2O2, ascorbate and metal ions
No full textMultiple electrophoretic bands, with RF identical to the natural molecular variants, are produced by treatment of purified Cu, Zn Superoxide dismutase with either H2O2 or ascorbate plus Fe(III) EDTA. The ascorbate reaction is also due to H2O2 since it is inhibited by catalase. However while H2O2 inactivates the enzyme, the electromorphs produced by ascorbate-Fe(III) EDTA have only slightly less activity than the native enzyme and this property parallels the natural situation. It is concluded that oxidative aging can be responsible for the multiple molecular variants of the natural enzyme, under conditions where the oxidant attack is preferentially directed to amino acid side chains outside the active site. Such conditions may occur when a metal ion coordinated to the protein surface undergoes a redox cycle with biological reductants, like ascorbate
Altered S-nitrosylation of p53 is responsible for impaired antioxidant response in skeletal muscle during aging
No full textp53 transcriptional activity has been proposed to regulate both homeostasis and sarcopenia of skeletal muscle during aging. However, the exact molecular function of p53 remains to be clearly defined. We demonstrated a requirement of nuclear p53 S-nitrosylation in inducing a nitric oxide/PGC-1α-mediated antioxidant pathway in skeletal muscle. Importantly, mutant form of p53-DNA binding domain (C124S) did not undergo nuclear S-nitrosylation and failed in inducing the expression of antioxidant genes (i.e. SOD2 and GCLC). Moreover, we found that during aging the nuclear S-nitrosylation of p53 significantly declines in gastrocnemius/soleus leading to an impairment of redox homeostasis of skeletal muscle. We suggested that decreased level of nuclear neuronal nitric oxide synthase (nNOS)/Syntrophin complex, which we observed during aging, could be responsible for impaired nuclear S-nitrosylation. Taken together, our data indicate that altered S-nitrosylation of p53 during aging could be a contributing factor of sarcopenia condition and of other skeletal muscle pathologies associated with oxidative/nitrosative stress
Redox control of apoptosis: An update
Full text linkThe redox environment of the cell is currently thought to be extremely important to control cell growth, differentiation, and apoptosis as many redox-sensitive proteins characterize these networks. A recent, widely accepted theory is that free radicals are not only dangerous species but, at low concentration, they have been designed by evolution to participate in the maintenance of cellular redox (reduction/oxidation) homeostasis. This notion derives from the evidence that cells constantly generate free radicals both as waste products of aerobic metabolism and in response to a large variety of stimuli. Free radicals, once produced, provoked cellular responses (redox regulation) against oxidative stress transducing the signals to maintain the cellular redox balance. Growing evidence suggests that in many instances the production of radical species is tightly regulated and their downstream targets are very specific, indicating that reactive oxygen species and reactive nitrogen species actively participate in several cell-signalling pathways as physiological "second messengers." In this review, we provide a general overview and novel insights into the redox-dependent pathways involved in programmed cell death. © Mary Ann Liebert, Inc
Reactive oxygen species-dependent c-Jun NH2-terminal kinase/c-Jun signaling cascade mediates neuroblastoma cell death induced by diallyl disulfide
Full text linkThe pharmacological properties of garlic and its derivatives are long known, and their underling mechanisms are being extensively investigated. In this study we have addressed the effects of diallyl disulfide (DADS), an oil-soluble garlic molecule, on cell growth of neuroblastoma cell SH-SY5Y, focusing on the redox events associated with this compound. Treatment of SH-SY5Y cells with DADS resulted in arrest of cell cycle in G(2)/M phase and commitment to apoptosis through the activation of the mitochondrial pathway (Bcl-2 down-regulation, cytochrome c release into the cytosol, and activation of caspase-9 and caspase-3). The earliest oxidative event observed after DADS treatment was the increase of production of reactive oxygen species, which reached the maximum yield on 30 min of DADS treatment. The oxidative burst resulted in protein and lipid damage as demonstrated by protein carbonyl accumulation and lipid peroxidation. We demonstrated that apoptosis induction was highly dependent on the activation of the redox-sensitive c-Jun NH2-terminal kinase (JNK)/c-jun pathway. In particular, we established that DADS treatment induces JNK dissociation from glutathione S-transferase and its activation by phosphorylation. Moreover, treatment with JNK inhibitor I significantly reduced DADS-induced apoptosis and treatment with the spin trap 5,5'-dimethyl-1-pyrroline N-oxide or overexpression of the antioxidant enzyme copper, zinc superoxide dismutase, resulted in the inhibition of DADS-mediated toxicity through attenuation of JNK/c-jun pathway activation. Overall, the results suggest a pivotal role for oxidative stress in DADS-induced apoptosis and, taking into account that tumor cells are deficient in antioxidants, suggest a plausible utilization of this compound as an antiproliferative agent in cancer therapy
Inactivation of erythrocyte glutathione peroxidase as a mechanism of red cell damage by hydroquinone and quinone drugs
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