Click chemistry-based thiol redox proteomics reveals significant cysteine reduction induced by chronic ethanol consumption

Harris, Peter; McGinnis, Courtney; Michel, Cole; Marentette, John; Reisdorph, Richard; Roede, James R.; Fritz, Kristofer S.

doi:10.1016/j.redox.2023.102792

Cited by 8 publications

(7 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Binding to IDH is confirmed by ESI-MS for 14 residues [155]. Since Lys212, His315, and Cys387 are essential for the activity of IDH2, an interaction with Hys and Cys is to be expected [85,86].…”

Section: Nadp + /Nadphmentioning

confidence: 82%

See 1 more Smart Citation

Lipid Peroxidation-Related Redox Signaling in Osteosarcoma

Borović Šunjić,

Jaganjac,

Vlainić

et al. 2024

IJMS

View full text Add to dashboard Cite

Oxidative stress and lipid peroxidation play important roles in numerous physiological and pathological processes, while the bioactive products of lipid peroxidation, lipid hydroperoxides and reactive aldehydes, act as important mediators of redox signaling in normal and malignant cells. Many types of cancer, including osteosarcoma, express altered redox signaling pathways. Such redox signaling pathways protect cancer cells from the cytotoxic effects of oxidative stress, thus supporting malignant transformation, and eventually from cytotoxic anticancer therapies associated with oxidative stress. In this review, we aim to explore the status of lipid peroxidation in osteosarcoma and highlight the involvement of lipid peroxidation products in redox signaling pathways, including the involvement of lipid peroxidation in osteosarcoma therapies.

show abstract

Section: Nadp + /Nadphmentioning

confidence: 82%

“…However, it can also bind directly to free GCLc and increase its catalytic activity [85]. In GCLc, Cys553 is activated by 4-HNE, but in the holoenzyme it is masked and 4-HNE cannot reach it, whereas Cys35 is exposed by GCLm [85,86].…”

Section: Gcl/gsh/gpx-gst Pathwaymentioning

confidence: 99%

Lipid Peroxidation-Related Redox Signaling in Osteosarcoma

Borović Šunjić,

Jaganjac,

Vlainić

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…Chronic ethanol consumption affects cardiac, hepatic, and urinary systems, as well as food and water intake in humans and rodents [49][50][51][52][53][54] . Therefore, we measured food and water intake, as well as liver, kidney, and heart masses.…”

Section: Discussionmentioning

confidence: 99%

Vascular injury associated with ethanol intake is driven by AT1 receptor and mitochondrial dysfunction

Awata,

Alves,

Costa

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Renin angiotensin (Ang II) aldosterone system (RAAS) is crucial for the cardiovascular risk associated with excessive ethanol consumption. Disturbs in mitochondria have been implicated in multiple cardiovascular diseases. However, if mitochondria dysfunction contributes to ethanol-induced vascular dysfunction is still unknown. We investigated whether ethanol leads to vascular dysfunction via RAAS activation, mitochondria dysfunction, and mitochondrial reactive oxygen species (mtROS). Methods: Male C57/BL6J or mt-keima mice (6 to 8-weeks old) were treated with ethanol (20% vol./vol.) for 12 weeks with or without Losartan (10 mg/kg). Results: Ethanol induced aortic hypercontractility in an endothelium-dependent manner. PGC1a; (a marker of biogenesis), Mfn2, (an essential protein for mitochondria fusion), as well as Pink-1 and Parkin (markers of mitophagy), were reduced in aortas from ethanol-treated mice. Disturb in mitophagy flux was further confirmed in arteries from mtkeima mice. Additionally, ethanol increased mtROS and reduced SOD2 expression. Strikingly, losartan prevented vascular hypercontractility, mitochondrial dysfunction, mtROS, and restored SOD2 expression. Both MnTMPyP (SOD2 mimetic) and CCCP (a mitochondrial uncoupler) reverted ethanol-induced vascular dysfunction. Moreover, L-NAME (NOS inhibitor) and EUK 134 (superoxide dismutase/catalase mimetic) did not affect vascular response in ethanol group, suggesting that ethanol reduces aortic nitric oxide (NO) and H2O2 bioavailability. These responses were prevented by losartan. Conclusion: AT1 receptor modulates ethanol-induced vascular hypercontractility by promoting mitochondrial dysfunction, mtROS, and reduction of NO and H2O2 bioavailability. Our findings shed a new light in our understanding of ethanol-induced vascular toxicity and open perspectives of new therapeutic approaches for patients with disorder associated with abusive ethanol drinking.

show abstract

“…36 This methodology has been used to demonstrate the absence of the Zn(II) ion in alcohol dehydrogenase 1 in a murine model of alcohol-associated liver disease. 19 Here, we developed an MS-based differential alkylation strategy to distinguish and map metalloform landscapes. As a representative model protein, we selected heterogeneous Cu(I)/Zn(II)-MT3, which has been previously demonstrated to exist as an air-stable Cu(I) 4 Zn(II) 3−4 MT3 complex when isolated from mammalian brains.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Cysteine, the most nucleophilic amino acid residue in proteins, is a target for reactive oxygen, nitrogen, and sulfur species and numerous chemical reactions, including post-translational, and critical for binding essential and toxic metal ions. − Recognizing the importance of Cys residues, a variety of experimental and theoretical tools have been developed to investigate the different redox states of Cys residues within proteomes, enabling a deeper understanding of their functional implications. − The detection and analysis of cysteine residues often rely on using thiol-specific probes that react with the nucleophilic sulfur of cysteine. , These probes exhibit different reactivity profiles, allowing for the differentiation of various forms and states of cysteine. Commonly employed protein thiol probes include iodoacetamide (IAM), iodoacetic acid (IAA), N -ethylmaleimide (NEM), methylmethanethiosulfonate (MMTS), Cys-reactive mass tag (cys-TMT), and p -benzoquinone (Bq). , IAM and NEM are widely used probes that covalently react with sulfhydryl groups using different mechanisms. , IAM undergoes S N 2 nucleophilic substitution, while NEM proceeds via nucleophilic Michael addition.…”

Section: Introductionmentioning

confidence: 99%

Combining Native Mass Spectrometry and Proteomics to Differentiate and Map the Metalloform Landscape in Metallothioneins

Peris-Díaz,

Orzeł,

et al. 2024

J. Proteome Res.

View full text Add to dashboard Cite

Within the intricate landscape of the proteome, approximately 30% of all proteins bind metal ions. This repertoire is even larger when considering all the different forms of a protein, known as proteoforms. Here, we propose the term "metalloforms" to refer to different structural or functional variations of a protein resulting from the binding of various hetero-or homogeneous metal ions. Using human Cu(I)/Zn(II)-metallothionein-3 as a representative model, we developed a chemical proteomics strategy to simultaneously differentiate and map Zn(II) and Cu(I) metal binding sites. In the first labeling step, Nethylmaleimide reacts with Cysteine (Cys), resulting in the dissociation of all Zn(II) ions while Cu(I) remains bound to the protein. In the second labeling step, iodoacetamide is utilized to label Cu(I)-bound Cys residues. Native mass spectrometry (MS) was used to determine the metal/labeling protein stoichiometries, while bottom-up/top-down MS was used to map the Cys-labeled residues. Next, we used a developed methodology to interrogate an isolated rabbit liver metallothionein fraction containing three metallothionein-2 isoforms and multiple Cd(II)/Zn(II) metalloforms. The approach detailed in this study thus holds the potential to decode the metalloproteoform diversity within other proteins.

show abstract

Click chemistry-based thiol redox proteomics reveals significant cysteine reduction induced by chronic ethanol consumption

Cited by 8 publications

References 65 publications

Lipid Peroxidation-Related Redox Signaling in Osteosarcoma

Lipid Peroxidation-Related Redox Signaling in Osteosarcoma

Vascular injury associated with ethanol intake is driven by AT1 receptor and mitochondrial dysfunction

Combining Native Mass Spectrometry and Proteomics to Differentiate and Map the Metalloform Landscape in Metallothioneins

Contact Info

Product

Resources

About