Abnormal proteins as the trigger for the induction of stress responses: Heat, diamide, and sodium arsenite

Lee, Kong Joo; Hahn, George M.

doi:10.1002/jcp.1041360304

Cited by 77 publications

(48 citation statements)

References 41 publications

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“…In the case of hHSF1, while it is clear that oxidation and intramolecular disulfide cross-link would stabilize the compact hHSF1 monomer and block its trimerization and activation, the effects of cysteine-SH oxidation in vivo are much more complex and likely involve multiple targets. For example, we observed that while diamide promoted the formation of ox-hHSF1 in HeLa cells, it also activated hHSF1, a result consistent with published observations (39,40). Furthermore, we showed in a previous study that thiol-reducing reagents inhibit the cellular heat shock response by blocking the activation, trimerization, and nuclear translocation of HSF1 (21).…”

Section: Discussionsupporting

confidence: 92%

“…However, these reagents (particularly diamide) caused activation of HSF1 DNA binding activity under a non-heat shock condition. In previous studies, diamide has been shown to induce the synthesis of heat shock proteins, presumably by producing oxidatively modified, abnormal proteins (39,40). This suggests that the effects of many of the oxidizing reagents in cells are complex due to their pleiotropic effect on the redox status of many cellular proteins.…”

Section: Figmentioning

confidence: 95%

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Resolution, Detection, and Characterization of Redox Conformers of Human HSF1

Manalo¹,

Liu

2001

Journal of Biological Chemistry

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We describe here an experimental protocol for the resolution, detection, and quantitation of the reduced and oxidized conformers of human heat shock factor 1 (hHSF1) and report on the effects in vitro and in vivo of redox-active agents on the redox status, structure, and function of hHSF1. We showed that diamide, a reagent that promotes disulfide bond formation, caused a loss of immunorecognition of the monomeric hHSF1 protein in a standard Western blot detection procedure. Modification of the Western blot procedure to include dithiothreitol in the equilibration and transfer buffers after gel electrophoresis allowed for the detection of a compact, intramolecularly disulfide cross-linked oxidized hHSF1 (ox-hHSF1) in the diamide-treated sample. The effect of diamide was blocked by pretreatment with N-ethylmaleimide and was reversed by dithiothreitol added to the sample prior to gel electrophoresis. Incubation with nitrosoglutathione at 42°C also promoted the conversion of HSF1 to ox-HSF1; at 25°C, however, nitrosoglutathione was by itself without effect but blocked the formation of ox-hHSF1 in the presence of diamide. The disulfide cross-linked ox-hHSF1 was monomeric and resistant to the in vitro heat-induced trimerization and activation. The possibility that ox-HSF1 may occur in oxidatively stressed cells was evaluated. Treatment of HeLa cells with 2 mM L-buthionine sulfoximine promoted the formation of ox-HSF1 and blocked the heatinduced activation of HSF DNA binding activity. Our result suggests that hHSF1 may have integrated redox chemistry of cysteine sulfhydryl into its functional responses.Cysteine, although not among the most common amino acid residues found in proteins, has unique chemical properties that confer upon it important and distinctive roles in protein structure and function. The free thiol group (S Ϫ , thiolate anion) of cysteine is a powerful nucleophile and is the most readily oxidized and nitrosylated of amino acid side chains (1, 2). The disulfide-bonded cystine, by comparison, is relatively unreactive but provides a covalent link between different regions of a protein and confers stability to a specific conformation (3, 4).These considerations gave impetus to the suggestion that the redox-dependent thiol-disulfide exchange reaction can provide an important mechanism to regulate protein structure and function (5, 6).The notion that thiol-disulfide exchange may be involved in regulating transcription factor activity has gained much recent interest and support (7). For example, activation of the prokaryotic OxyR transcription factor has been shown to be a two-step process involving first the oxidation of Cys-199 to a sulfenic acid followed by intramolecular disulfide cross-link of . Importantly, OxyR can be activated independently by hydrogen peroxide or by a shift of the cellular redox state as in Escherichia coli mutants lacking components of the thioredoxin and glutaredoxin pathways (9). These observations provided the much needed information to relate changes in cellular redox status to t...

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Section: Discussionsupporting

confidence: 92%

Section: Figmentioning

confidence: 95%

Resolution, Detection, and Characterization of Redox Conformers of Human HSF1

Manalo¹,

Liu

2001

Journal of Biological Chemistry

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“…When administered at non-lethal concentrations SA induces synthesis of a specific class of proteins, known as heat shock proteins (Hsps) and development of tolerance (Lee and Hahn, 1988;Nover, 1991;Welch, 1992). The phenomenon of SA-induced tolerance is described as a stress-induced cellular resistance to a lethal stress treatment (Wiegant et al, 1993).…”

Section: Inflammatory Bowel Diseases (Ibd) That Includementioning

confidence: 99%

Sodium arsenite reduces severity of dextran sulfate sodium-induced ulcerative colitis in rats

Malago

Nondoli²

2008

J. Zhejiang Univ. Sci. B

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Abstract:The histopathological features and the associated clinical findings of ulcerative colitis (UC) are due to persistent inflammatory response in the colon mucosa. Interventions that suppress this response benefit UC patients. We tested whether sodium arsenite (SA) benefits rats with dextran sulfate sodium (DSS)-colitis. The DSS-colitis was induced by 5% DSS in drinking water. SA (10 mg/kg; intraperitoneally) was given 8 h before DSS treatment and then every 48 h for 3 cycles of 7, 14 or 21 d. At the end of each cycle rats were sacrificed and colon sections processed for histological examination. DSS induced diarrhea, loose stools, hemoccult positive stools, gross bleeding, loss of body weight, loss of epithelium, crypt damage, depletion of goblet cells and infiltration of inflammatory cells. The severity of these changes increased in the order of Cycles 1, 2 and 3. Treatment of rats with SA significantly reduced this severity and improved the weight gain.

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“…Thus, the iron-mediated stress response seen in this study may be the result of free radical-mediated damage. Free radicals may induce a stress response by causing altered intracellular calcium concentrations (Keith et al, 1983;Lamarche et al, 1985), a lowering of intracellular pH (Weitzel et al, 1987;Nishimura et al, 1989), protein phosphorylation (Henle et al,I990), and production of abnormal proteins (Hightower, 1980;Ananthan et al, 1986;Lee and Hahn, 1988).…”

Section: Discussionmentioning

confidence: 99%

Changes in Heat Shock Protein 70 and Ubiquitin mRNA Levels in C1300 N2A Mouse Neuroblastoma Cells Following Treatment with Iron

Uney

Anderton

Thomas

1993

Journal of Neurochemistry

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Abstract:We have shown that following heat shock (42.5"C for 30 min), mouse-derived C 1300 N2A neuroblastoma cells contain increased levels of mRNA coding for the inducible form of heat shock protein 70 and for ubiquitin. Incubation of C1300 cells with iron also induces an elevation in content of mRNAs coding for the same two proteins that can be blocked by a-tocopherol and desfemoxamine. Iron was shown to increase mitochondria1 and lysosomal activities in differentiated C1300 N2A cultures, as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and neutral red cytotoxicity assays. These responses were not initially associated with any loss of viability, as assessed by the lactate dehydrogenase release assay. These results suggest that there is production of cytoprotective heat shock proteins in response to iron-mediated cell damage, probably involving free radical generation, in neural cells. The apparent stress response of vulnerable neurones in human neurodegenerative diseases, particularly Parkinson's disease, may be induced by iron-mediated free radical production in degenerating neurones, making investigation of the mechanism of free radical-induced responses in neuronal cells of special interest.

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Abnormal proteins as the trigger for the induction of stress responses: Heat, diamide, and sodium arsenite

Cited by 77 publications

References 41 publications

Resolution, Detection, and Characterization of Redox Conformers of Human HSF1

Resolution, Detection, and Characterization of Redox Conformers of Human HSF1

Sodium arsenite reduces severity of dextran sulfate sodium-induced ulcerative colitis in rats

Changes in Heat Shock Protein 70 and Ubiquitin mRNA Levels in C1300 N2A Mouse Neuroblastoma Cells Following Treatment with Iron

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