Trifluoroethanol increases albumin’s susceptibility to chemical modification

Craig, Heather D.; Eklund, Joshua D.; Seidler, Norbert W.

doi:10.1016/j.abb.2008.09.009

Cited by 10 publications

(8 citation statements)

References 45 publications

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“…We know that aB-crystallin protects against hypertonic stress [24]. Furthermore, a-crystallin has an additional moonlighting function as an antiglycation agent [25], which is consistent with the previously observed increase in aldehydic modification of proteins exposed to inhaled anesthetics [4,5,26], suggesting that anesthetic preconditioning may confer protection against future glycation stress. The mechanism of isoflurane-induced protein misfolding seen previously [3] may involve a localized dehydration of protein, which consequently may increase the susceptibility to aggregation.…”

Section: Discussionsupporting

confidence: 80%

“…The mechanism of isoflurane-induced protein misfolding seen previously [3] may involve a localized dehydration of protein, which consequently may increase the susceptibility to aggregation. Upon binding and release, there may be a desolvation or change in the hydration at the isoflurane binding site [27], resulting in altered protein conformation [3,5,26] and changes in protein-protein interaction [4]. Ethanol also displaces water from protein sites [28,29].…”

Section: Discussionmentioning

confidence: 98%

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Protection Against Protein Aggregation by Alpha-Crystallin as a Mechanism of Preconditioning

et al. 2011

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Anesthetic preconditioning occurs when cells previously exposed to inhaled anesthetics are protected against subsequent injury. We hypothesize that inhaled anesthetics may cause slight protein misfolding that involves site-specific dehydration, stimulating cytoprotective mechanisms. Human neuroblastoma cells were exposed to ethanol (as the dehydration agent) followed by quantitative analysis of the expression of five heat shock genes: DNAJC5G, CRYAA, HSPB2, HSF4 and HSF2. There was an ethanol-induced upregulation of all genes except HSF4, similar to previous observations using isoflurane. CRYAA (the gene for alphaA-crystallin) exhibited a 23.19 and 17.15-fold increase at 24 and 48 h post ethanol exposure, respectively. Additionally, we exposed glyceraldehyde 3-phosphate dehydrogenase to ethanol, which altered oligomeric subspecies and caused protein aggregation in a concentration-dependent manner. Ethanol-mediated dehydration-induced protein aggregation was prevented by incubation with alpha-crystallin. These data indicate that ethanol mimics the effects of isoflurane presumably through a cellular preconditioning mechanism that involves dehydration-induced protein aggregation.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 98%

Protection Against Protein Aggregation by Alpha-Crystallin as a Mechanism of Preconditioning

et al. 2011

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“…HSA was also used as a model for studying the effects of inhaled anaesthetics on the ability of ACR to chemically modify human serum albumin [63], with the final aim of understanding the mechanisms associated with (or causing) postoperative cognitive dysfunction, a side effect of surgery and anaesthesia particularly in the older population. This is because aldehyde-mediated modification is dependent on the folded state of the protein, and protein conformation may be influenced by inhaled anaesthetics.…”

Section: In Vitro Evidencementioning

confidence: 99%

Protein modification by acrolein: Relevance to pathological conditions and inhibition by aldehyde sequestering agents

Aldini

Orioli

Carini

2011

Molecular Nutrition Food Res

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Acrolein (ACR) is a toxic and highly reactive α,β-unsaturated aldehyde widely distributed in the environment as a common pollutant and generated endogenously mainly by lipoxidation reactions. Its biological effects are due to its ability to react with the nucleophilic sites of proteins, to form covalently modified biomolecules which are thought to be involved as pathogenic factors in the onset and progression of many pathological conditions such as cardiovascular and neurodegenerative diseases. Functional impairment of structural proteins and enzymes by covalent modification (crosslinking) and triggering of key cell signalling systems are now well-recognized signs of cell and tissue damage induced by reactive carbonyl species (RCS). In this review, we mainly focus on the in vitro and in vivo evidence demonstrating the ability of ACR to covalently modify protein structures, in order to gain a deeper insight into the dysregulation of cellular and metabolic pathways caused by such modifications. In addition, by considering RCS and RCS-modified proteins as drug targets, this survey will provide an overview on the newly developed molecules specifically tested for direct or indirect ACR scavenging, and the more significant studies performed in the last years attesting the efficacy of compounds already recognized as promising aldehyde-sequestering agents.

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“…We previously observed that isoflurane increased the susceptibility of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) to MG-induced modification [9]. Acrolein-induced modification of HSA was also promoted by trifluoroethanol that is used to mimic the effects of inhaled anesthetics on protein structure [8]. Our observations with MG represent modifications of residues that are rather accessible, suggesting that they are exposed to solvent and likely on the surface of the protein.…”

Section: Resultsmentioning

confidence: 67%

“…The susceptibility of proteins to chemical modification by carbohydrate and lipid fragmentation products increases following exposure to inhaled anesthetics [8, 9]. The current study further explores the consequence of isoflurane binding using serum albumin as a surrogate protein in order to elucidate the effects of inhaled anesthetics on protein conformation.…”

Section: Introductionmentioning

confidence: 99%

Isoflurane's Effect on Protein Conformation as a Proposed Mechanism for Preconditioning

Baker

Benton

Theisen

et al. 2011

Biochemistry Research International

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Persistent alteration of protein conformation due to interaction with isoflurane may be a novel molecular aspect of preconditioning. We preincubated human serum albumin with isoflurane, dialyzed to release agent, and assessed protein conformation. Susceptibility to chemical modification by methylglyoxal and nitrophenylacetate was also examined. Isoflurane had a persistent effect on protein conformation. An increase in the susceptibility of surface residues to chemical modification attended this change in conformation. Modification of isoflurane-treated HSA included intra- and intersubunit cross-linking that may be a consequence of anesthetic-induced changes in multimeric subpopulations. This irreversible effect of isoflurane may represent a mechanism for preconditioning.

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Trifluoroethanol increases albumin’s susceptibility to chemical modification

Cited by 10 publications

References 45 publications

Protection Against Protein Aggregation by Alpha-Crystallin as a Mechanism of Preconditioning

Protection Against Protein Aggregation by Alpha-Crystallin as a Mechanism of Preconditioning

Protein modification by acrolein: Relevance to pathological conditions and inhibition by aldehyde sequestering agents

Isoflurane's Effect on Protein Conformation as a Proposed Mechanism for Preconditioning

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