Inactivation of glutathione reductase by 4-hydroxynonenal and other endogenous aldehydes

Jagt, David L. Vander; Hunsaker, Lucy A.; Jagt, Timothy J. Vander; Gomez, Manuel S.; Gonzales, Donna M.; Deck, Lorraine M.; Royer, Robert E.

doi:10.1016/s0006-2952(97)00090-7

Cited by 140 publications

(74 citation statements)

References 27 publications

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“…Our interpretation is in line with recent works reporting that dicarbonyl compounds, such as methylglyoxal, easily react with intracellular proteins resulting in intracellular AGE formation, which is associated with alterations of protein structure and function (48,49). By doing so, methylglyoxal affects cellular responses (46,49). It should be mentioned that it is likely that methylglyoxal interferes with additional actors in the insulin signaling pathway.…”

Section: Discussionsupporting

confidence: 91%

“…The cytotoxic action occurs mainly through the induction of ROS, and methylglyoxal can increase oxidative stress by inactivating glutathion reductase (46). Therefore, the alterations in insulin-stimulated signaling pathways that we observed after methylglyoxal treatment could be due to the molecular modifications induced by methylglyoxal and to the consequences of ROS production and/or methylglyoxal cytotoxicity.…”

Section: Discussionmentioning

confidence: 81%

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Methylglyoxal Impairs the Insulin Signaling Pathways Independently of the Formation of Intracellular Reactive Oxygen Species

et al. 2006

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Nonenzymatic glycation is increased in diabetes and leads to elevated levels of advanced glycation end products (AGEs), which link hyperglycemia to the induction of insulin resistance. In hyperglycemic conditions, intracellularly formed ␣-ketoaldehydes, such as methylglyoxal, are an essential source of intracellular AGEs, and the abnormal accumulation of methylglyoxal is related to the development of diabetes complications in various tissues and organs. We have previously shown in skeletal muscle that AGEs induce insulin resistance at the level of metabolic responses. Therefore, it was important to extend our work to intermediates of the biosynthetic pathway leading to AGEs. Hence, we asked the question whether the reactive ␣-ketoaldehyde methylglyoxal has deleterious effects on insulin action similar to AGEs. We analyzed the impact of methylglyoxal on insulin-induced signaling in L6 muscle cells. We demonstrate that a short exposure to methylglyoxal induces an inhibition of insulin-stimulated phosphorylation of protein kinase B and extracellular-regulated kinase 1/2, without affecting insulin receptor tyrosine phosphorylation. Importantly, these deleterious effects of methylglyoxal are independent of reactive oxygen species produced by methylglyoxal but appear to be the direct consequence of an impairment of insulin-induced insulin receptor substrate-1 tyrosine phosphorylation subsequent to the binding of methylglyoxal to these proteins. Our data suggest that an increase in intracellular methylglyoxal content hampers a key molecule, thereby leading to inhibition of insulin-induced signaling. By such a mechanism, methylglyoxal may not only induce the debilitating complications of diabetes but may also contribute to the pathophysiology of diabetes in general.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 81%

Methylglyoxal Impairs the Insulin Signaling Pathways Independently of the Formation of Intracellular Reactive Oxygen Species

et al. 2006

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“…50) Acrolein also induces the polymerization of actin, and the formation of His adducts distorts the ATP-binding site of actin, damaging the cytoskeleton. 51) Furthermore, glutathione reductase is inactivated by acrolein-dependent modification of Cys. 30) Finally, acrolein forms conjugates with glutathione GSH, which lowers the antioxidant activity of GSH.…”

Section: Discussionmentioning

confidence: 99%

“…51) Furthermore, glutathione reductase is inactivated by acrolein-dependent modification of Cys. 30) Finally, acrolein forms conjugates with glutathione GSH, which lowers the antioxidant activity of GSH. 17) Acrolein also inactivates the Benson-Calvin cycle enzymes phosphoribulokinase (PRK) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH).…”

Section: Discussionmentioning

confidence: 99%

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Acrolein, an α,β-Unsaturated Carbonyl, Inhibits Both Growth and PSII Activity in the CyanobacteriumSynechocystissp. PCC 6803

Shimakawa

Iwamoto

Mabuchi

et al. 2013

Bioscience, Biotechnology, and Biochemistry

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Getting the Message? Native Reactive Electrophiles Pass Two Out of Three Thresholds to be Bona Fide Signaling Mediators

2018

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Precision cell signaling activities of reactive electrophilic species (RES) are arguably among the most poorly-understood means to transmit biological messages. Latest research implicates native RES to be a chemically-distinct subset of endogenous redox signals that influence cell decision making through non-enzyme-assisted modifications of specific proteins. Yet, fundamental questions remain regarding the role of RES as bona fide second messengers. Here, we lay out three sets of criteria we feel need to be met for RES to be considered as true cellular signals that directly mediate information transfer by modifying "first-responding" sensor proteins. We critically assess the available evidence and define the extent to which each criterion has been fulfilled. Finally, we offer some ideas on the future trajectories of the electrophile signaling field taking inspiration from work that has been done to understand canonical signaling mediators. Also see the video abstract here: https://youtu.be/rG7o0clVP0c.

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Inactivation of glutathione reductase by 4-hydroxynonenal and other endogenous aldehydes

Cited by 140 publications

References 27 publications

Methylglyoxal Impairs the Insulin Signaling Pathways Independently of the Formation of Intracellular Reactive Oxygen Species

Methylglyoxal Impairs the Insulin Signaling Pathways Independently of the Formation of Intracellular Reactive Oxygen Species

Acrolein, an α,β-Unsaturated Carbonyl, Inhibits Both Growth and PSII Activity in the CyanobacteriumSynechocystissp. PCC 6803

Getting the Message? Native Reactive Electrophiles Pass Two Out of Three Thresholds to be Bona Fide Signaling Mediators

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