Modulation of the redox state of tubulin by the glutathione/glutaredoxin reductase system

Landino, Lisa M.; Moynihan, Katherine L.; Todd, Jonathan; Kennett, Kelly L

doi:10.1016/j.bbrc.2003.12.126

Cited by 96 publications

(72 citation statements)

References 22 publications

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“…Tubulin is a cysteine-rich redox-sensitive protein that plays a crucial function in cell division. Modification of tubulin redox state or alkylation of functional sulfhydryl groups may lead to impairment of microtubule polymerization and inhibition of cellular proliferation (42). This feature has been exploited for the development of anticancer agents (43,44).…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Protein Targets for Modification by 15-Deoxy-Δ12,14-Prostaglandin J2 in Mesangial Cells Reveals Multiple Interactions with the Cytoskeleton

Stamatakis¹,

Sánchez‐Gómez²

2006

Journal of the American Society of Nephrology

108

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The cyclopentenone prostaglandin 15-deoxy-⌬ 12,14 -PGJ 2 (15d-PGJ 2 ) has been shown to display protective effects against renal injury or inflammation. In cultured mesangial cells (MC), 15d-PGJ 2 inhibits the expression of proinflammatory genes and modulates cell proliferation. Therefore, cyclopentenone prostaglandins (cyPG) have been envisaged as a promise in the treatment of renal disease. The effects of 15d-PGJ 2 may be dependent on or independent from its role as a peroxisome proliferator-activated receptor agonist. It was shown recently that an important determinant for the peroxisome proliferatoractivated receptor-independent effects of 15d-PGJ 2 is the capacity to modify proteins covalently and alter their function. However, a limited number of protein targets have been identified to date. Herein is shown that a biotinylated derivative of 15d-PGJ 2 recapitulates the effects of 15d-PGJ 2 on the stress response and inhibition of inducible nitric oxide synthase levels and forms stable adducts with proteins in intact MC. Biotinylated 15d-PGJ 2 was then used to identify proteins that potentially are involved in cyPG biologic effects. Extracts from biotinylated 15d-PGJ 2 -treated MC were separated by two-dimensional electrophoresis, and the spots of interest were analyzed by mass spectrometry. Identified targets include proteins that are regulated by oxidative stress, such as heat-shock protein 90 and nucleoside diphosphate kinase, as well as proteins that are involved in cytoskeletal organization, such as actin, tubulin, vimentin, and tropomyosin. Biotinylated 15d-PGJ 2 binding to several targets was confirmed by avidin pull-down. Consistent with these findings, 15d-PGJ 2 induced early reorganization of vimentin and tubulin in MC. The cyclopentenone moiety and the presence of cysteine were important for vimentin rearrangement. These studies may contribute to the understanding of the mechanism of action and therapeutic potential of cyPG.

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Section: Discussionmentioning

confidence: 99%

Identification of Novel Protein Targets for Modification by 15-Deoxy-Δ12,14-Prostaglandin J2 in Mesangial Cells Reveals Multiple Interactions with the Cytoskeleton

Stamatakis¹,

Sánchez‐Gómez²

2006

Journal of the American Society of Nephrology

108

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“…One potential explanation for this proliferation of tubulin isoforms could lay in the upregulation of formylglutathione hydrolase at 13°C, an enzyme that produces glutathione. Protein glutathionylation is an important and widespread reaction to protect sulfhydryl groups (Dalle-Donne et al, 2009), specifically in tubulins (Landino et al, 2004).…”

Section: Cold Acclimationmentioning

confidence: 99%

Proteomic responses of blue mussel (Mytilus) congeners to temperature acclimation

Fields

Zuzow

Tomanek

2012

Journal of Experimental Biology

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SUMMARYThe ability to acclimate to variable environmental conditions affects the biogeographic range of species, their success at colonizing new habitats, and their likelihood of surviving rapid anthropogenic climate change. Here we compared responses to temperature acclimation (4weeks at 7, 13 and 19°C) in gill tissue of the warm-adapted intertidal blue mussel Mytilus galloprovincialis, an invasive species in the northeastern Pacific, and the cold-adapted M. trossulus, the native congener in the region, to better understand the physiological differences underlying the ongoing competition. Using two-dimensional gel electrophoresis and tandem mass spectrometry, we showed that warm acclimation caused changes in cytoskeletal composition and proteins of energy metabolism in both species, consistent with increasing rates of filtration and respiration due to increased ciliary activity. During cold acclimation, changes in cytoskeletal proteins were accompanied by increasing abundances of oxidative stress proteins and molecular chaperones, possibly because of the increased production of aldehydes as indicated by the upregulation of aldehyde dehydrogenase. The cold-adapted M. trossulus showed increased abundances of molecular chaperones at 19°C, but M. galloprovincialis did not, suggesting that the two species differ in their long-term upper thermal limits. In contrast, the warm-adapted M. galloprovincialis showed a stronger response to cold acclimation than M. trossulus, including changes in abundance in more proteins and differing protein expression profiles between 7 and 13°C, a pattern absent in M. trossulus. In general, increasing levels of oxidative stress proteins inversely correlate with modifications in Krebs cycle and electron transport chain proteins, indicating a trade-off between oxidative stress resistance and energy production. Overall, our results help explain why M. galloprovincialis has replaced M. trossulus in southern California over the last century, but also suggest that M. trossulus may maintain a competitive advantage at colder temperatures. Anthropogenic global warming may reinforce the advantage M. galloprovincialis has over M. trossulus in the warmer parts of the latterʼs historical range. Supplementary material available online at

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“…GRX1 and S-glutathionylation are thought to be involved in a variety of cellular events such as signal transduction, stress response, and metabolic regulation, by regulating the redox status of various cellular proteins, including HIV-1 protease 16) , glyceraldehyde-3-phosphate dehydrogenase (GAPDH) 17) , nuclear factor I 18) , ASK1 19) , actin 20) , Ras 21) , tubulin 22) , tau and microtubule-associated protein-2 23) , annexin A2 24) , and protein tyrosine phosphatase 1B 25) . We have also reported that GRX plays an important role in protecting cells from apoptosis by regulating the redox status of Akt/protein kinase B 26) .…”

Section: Introductionmentioning

confidence: 99%

Roles of Oxidative Stress and Redox Regulation in Atherosclerosis

Kondo

Hirose

Kageyama

2009

JAT

120

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Oxidative stress is believed to be a cause of aging and cardiovascular disorders. In response to inflammation or endothelial cell injury, production of reactive oxygen species (ROS) is enhanced in vascular cells. These changes contribute to the initiation of atherosclerosis. Vascular cells possess anti-oxidant systems to protect against oxidative stress, in addition to the redox system. The redox status of protein thiols is important for cellular functions. The Akt signaling pathway exerts effects on survival and apoptosis, and is regulated by the glutathione (GSH)/glutaredoxin (GRX)-dependent redox system. Sex hormones such as estrogens protect against oxidative stress by protecting the Akt signaling pathway but the physiological role of the extracellular GSH/GRX system has not been clarified, although found an increase in the levels of S-glutathionylated serum proteins in patients with atherosclerosis obliterans. The results suggested that impaired serum redox potential is a marker of the development vascular dysfunction and estrogen has a possible role in the prevention of atherosclerosis. eNOS and its level is regulated by guanosine triphosphate cyclohydrolase 1, a rate-limiting enzyme in BH4 synthesis, and the redox state of BH4. Under oxidative stress, BH4 is oxidized to form 7,8-dihydropterin (BH2) and biopterin, both incapable of eNOS catalysis. The redox regulation of BH4 and BH2 seems clinically important, although, the precise mechanism is not clear 6,7)

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Modulation of the redox state of tubulin by the glutathione/glutaredoxin reductase system

Cited by 96 publications

References 22 publications

Identification of Novel Protein Targets for Modification by 15-Deoxy-Δ12,14-Prostaglandin J2 in Mesangial Cells Reveals Multiple Interactions with the Cytoskeleton

Identification of Novel Protein Targets for Modification by 15-Deoxy-Δ12,14-Prostaglandin J2 in Mesangial Cells Reveals Multiple Interactions with the Cytoskeleton

Proteomic responses of blue mussel (Mytilus) congeners to temperature acclimation

Roles of Oxidative Stress and Redox Regulation in Atherosclerosis

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