Cellular and Environmental Electrophiles: Balancing Redox Signaling, Inflammation, and Cell Death Pathways

Vliet, Albert van der; Hristova, Milena; McCarthy, Sean M.; Kasahara, David I.

doi:10.1007/978-1-4020-8399-0_3

Cited by 3 publications

(2 citation statements)

References 164 publications

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“…The cellular response to protein oxidation and electrophilic stress is conserved throughout evolution and results in decreased proliferation and/or cytotoxicity due to necrosis or apoptosis [ [36] , [37] , [38] , [39] ]. Our study shows that cysteine trisulfide induced electrophilic stress and inhibited proliferation in human cell lines, similar to diallyl trisulfide and dibenzyl trisulfide [ [40] , [41] , [42] , [43] , [44] ].…”

Section: Discussionmentioning

confidence: 99%

Cysteine trisulfide oxidizes protein thiols and induces electrophilic stress in human cells

et al. 2021

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The cellular effects of hydrogen sulfide (H 2 S) signaling may be partially mediated by the formation of alkyl persulfides from thiols, such as glutathione and protein cysteine residues. Persulfides are potent nucleophiles and reductants and therefore potentially an important endogenous antioxidant or protein post-translational modification. To directly study the cellular effects of persulfides, cysteine trisulfide (Cys-S 3 ) has been proposed as an in situ persulfide donor, as it reacts with cellular thiols to generate cysteine persulfide (Cys-S-S − ). Numerous pathways sense and respond to electrophilic cellular stressors to inhibit cellular proliferation and induce apoptosis, however the effect of Cys-S 3 on the cellular stress response has not been addressed. Here we show that Cys-S 3 inhibited cellular metabolism and proliferation and rapidly induced cellular- and ER-stress mechanisms, which were coupled to widespread protein-thiol oxidation. Cys-S 3 reacted with Na 2 S to generate cysteine persulfide, which protected human cell lines from ER-stress. However this method of producing cysteine persulfide contains excess sulfide, which interferes with the direct analysis of persulfide donation. We conclude that cysteine trisulfide is a thiol oxidant that induces cellular stress and decreased proliferation.

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Section: Discussionmentioning

confidence: 99%

Cysteine trisulfide oxidizes protein thiols and induces electrophilic stress in human cells

et al. 2021

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“…These RAs are environmental pollutants but can also be endogenously produced from lipid oxidation. 15 At biological/cellular concentrations, these RAs induce various stress responses, and can activate or inactivate signaling pathways that are involved in transcription factor activation and regulation of gene expression. Their effects ultimately determine cellular fates, such as the production of cellular inflammatory mediators, or cell proliferation, survival, or apoptosis.…”

Section: Electrophilic Ras As Biological Mediatorsmentioning

confidence: 99%

GSTM1 Gene, Diet, and Kidney Disease: Implication for Precision Medicine?: Recent Advances in Hypertension

2021

Hypertension

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In the United States, the prevalence of chronic kidney disease in adults is ≈14%. The mainstay of therapy for chronic kidney disease is angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, but many patients with chronic kidney disease still progress to end-stage kidney disease. Increased oxidative stress is a major molecular underpinning of chronic kidney disease progression. In humans, a common deletion variant of the glutathione-S-transferase μ-1 ( GSTM1 ) gene, the GSTM1 null allele ( GSTM1(0 )), results in decreased GSTM1 enzymatic activity and is associated with higher levels of oxidative stress. GSTM1 belongs to the superfamily of GSTs that are phase II antioxidant enzymes and are regulated by Nrf2 (nuclear factor erythroid 2-related factor 2). Cruciferous vegetables in general, and broccoli in particular, are rich in glucoraphanin, a precursor of sulforaphane that has been shown to have protective effects against oxidative damage through the activation of Nrf2. This review will highlight recent human and animal studies implicating the role of GSTM1 deficiency in hypertension and kidney disease, and its impact on the effects of cruciferous vegetables on kidney injury and disease progression, illustrating the significance of gene and environment interaction and a potential for targeted precision medicine in the treatment of kidney disease.

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Insights on the mechanisms of action of ozone in the medical therapy against COVID-19

Chirumbolo

Valdenassi

Simonetti

et al. 2021

International Immunopharmacology

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An increasing amount of reports in the literature is showing that medical ozone (O 3 ) is used, with encouraging results, in treating COVID-19 patients, optimizing pain and symptoms relief, respiratory parameters, inflammatory and coagulation markers and the overall health status, so reducing significantly how much time patients underwent hospitalization and intensive care. To date, aside from mechanisms taking into account the ability of O 3 to activate a rapid oxidative stress response, by up-regulating antioxidant and scavenging enzymes, no sound hypothesis was addressed to attempt a synopsis of how O 3 should act on COVID-19. The knowledge on how O 3 works on inflammation and thrombosis mechanisms is of the utmost importance to make physicians endowed with new guns against SARS-CoV2 pandemic. This review tries to address this issue, so to expand the debate in the scientific community.

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Cellular and Environmental Electrophiles: Balancing Redox Signaling, Inflammation, and Cell Death Pathways

Cited by 3 publications

References 164 publications

Cysteine trisulfide oxidizes protein thiols and induces electrophilic stress in human cells

Cysteine trisulfide oxidizes protein thiols and induces electrophilic stress in human cells

GSTM1 Gene, Diet, and Kidney Disease: Implication for Precision Medicine?: Recent Advances in Hypertension

Insights on the mechanisms of action of ozone in the medical therapy against COVID-19

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