Detection, identification, and quantification of oxidative protein modifications

Journal of Biological Chemistry, Journal Year: 2019, Volume and Issue: 294(51), P. 19683 - 19708

Published: Oct. 31, 2019

Exposure of biological molecules to oxidants is inevitable and therefore commonplace. Oxidative stress in cells arises from both external agents endogenous processes that generate reactive species, either purposely (e.g. during pathogen killing or enzymatic reactions) accidentally exposure radiation, pollutants, drugs, chemicals). As proteins are highly abundant react rapidly with many oxidants, they susceptible to, major targets of, oxidative damage. This can result changes protein structure, function, turnover loss (occasional) gain activity. Accumulation oxidatively-modified proteins, due increased generation decreased removal, has been associated aging multiple diseases. Different a broad, sometimes characteristic, spectrum post-translational modifications. The kinetics (rates) damage formation also vary dramatically. There pressing need for reliable robust methods detect, identify, quantify the products formed on amino acids, peptides, especially complex systems. review summarizes several advances our understanding this chemistry highlights available detect modifications—at acid, peptide, level—and their nature, quantity, position within peptide sequence. Although considerable progress made development application new techniques, it clear further required fully assess relative importance oxidation determine whether an cause, merely consequence, injurious processes.

Language: Английский

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Physiological roles of hydrogen sulfide in mammalian cells, tissues, and organs

Physiological Reviews, Journal Year: 2022, Volume and Issue: 103(1), P. 31 - 276

Published: April 18, 2022

Over the last two decades, hydrogen sulfide (H2S) has emerged as an endogenous regulator of a broad range physiological functions. H2S belongs to class molecules known gasotransmitters, which typically include nitric oxide (NO) and carbon monoxide (CO). Three enzymes are recognized sources in various cells tissues: cystathionine γ-lyase (CSE), β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MST). The present article reviews regulation these well pathways their enzymatic nonenzymatic degradation elimination. multiple interactions with other labile (e.g., NO) reactive oxygen species also outlined. Next, biological targets signaling outlined, special reference or oxidative posttranscriptional modification (persulfidation sulfhydration) proteins effect on channels intracellular second messenger pathways, gene transcription translation, cellular bioenergetics metabolism. pharmacological molecular tools currently available study physiology reviewed, including utility limitations. In subsequent sections, role functions is membrane potential, endo- exocytosis, cell organelles (endoplasmic reticulum, Golgi, mitochondria), movement, cycle, differentiation, aspects regulated death. roles types organ systems overviewed, red blood cells, immune central peripheral nervous (with focus neuronal transmission, learning, memory formation), vascular function (including angiogenesis its specialized cerebrovascular, renal, pulmonary beds) senses, vision, hearing, taste smell, pain-sensing. Finally, (lung, heart, liver, kidney, urogenital organs, reproductive system, bone cartilage, skeletal muscle, endocrine organs) presented, aging) but extending some common pathophysiological conditions. From data, wide array significant all emerges characteristic bell-shaped biphasic effects highlighted. addition, key aspects, debated areas, future research translational areas identified.

Language: Английский

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Regulators of the transsulfuration pathway

British Journal of Pharmacology, Journal Year: 2018, Volume and Issue: 176(4), P. 583 - 593

Published: July 14, 2018

The transsulfuration pathway is a metabolic where transfer of sulfur from homocysteine to cysteine occurs. leads the generation several metabolites, which include cysteine, GSH and gaseous signalling molecule hydrogen sulfide (H

Language: Английский

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Cysteine Metabolism in Neuronal Redox Homeostasis

Trends in Pharmacological Sciences, Journal Year: 2018, Volume and Issue: 39(5), P. 513 - 524

Published: March 9, 2018

Language: Английский

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Hydrogen sulfide: An endogenous regulator of the immune system

Pharmacological Research, Journal Year: 2020, Volume and Issue: 161, P. 105119 - 105119

Published: Aug. 8, 2020

Hydrogen sulfide (H2S) is now recognized as an endogenous signaling gasotransmitter in mammals. It produced by mammalian cells and tissues various enzymes - predominantly cystathionine β-synthase (CBS), γ-lyase (CSE) 3-mercaptopyruvate sulfurtransferase (3-MST) but part of the H2S intestinal microbiota (colonic H2S-producing bacteria). Here we summarize available information on production functional role cell types typically associated with innate immunity (neutrophils, macrophages, dendritic cells, natural killer mast basophils, eosinophils) adaptive (T B lymphocytes) under normal conditions it relates to development inflammatory immune diseases. Special attention paid physiological pathophysiological aspects oral cavity colon, where parenchymal are exposed a special "H2S environment" due bacterial production. has many cellular molecular targets. Immune "surrounded" "cloud" H2S, result exogenous from surrounding which, turn, importantly regulates their viability function. Downregulation producing diseases, or genetic defects biosynthetic enzyme systems either lead spontaneous autoimmune disease accelerate onset worsen severity immune-mediated diseases (e.g. rheumatoid arthritis asthma). Low, regulated amounts when therapeutically delivered small molecule donors, improve function protect them against dysfunction induced noxious stimuli reactive oxygen species oxidized LDL). These effects contribute maintenance functions, can stimulate antimicrobial defenses exert anti-inflammatory therapeutic

Language: Английский

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Hydrogen sulfide signaling in mitochondria and disease

The FASEB Journal, Journal Year: 2019, Volume and Issue: 33(12), P. 13098 - 13125

Published: Oct. 24, 2019

Hydrogen sulfide can signal through 3 distinct mechanisms: 1) reduction and/or direct binding of metalloprotein heme centers, 2) serving as a potent antioxidant reactive oxygen species/reactive nitrogen species scavenging, or 3) post‐translational modification proteins by addition thiol (‐SH) group onto cysteine residues: process known persulfidation. Below toxic levels, hydrogen promotes mitochondrial biogenesis and function, thereby conferring protection against cellular stress. For these reasons, increases in sulfide‐producing enzymes have been implicated several human disease states. This review will first summarize our current understanding production metabolism, well its signaling mechanisms; second, this work detail the mechanisms mitochondria implications mitochondrial‐specific impacts pathologic conditions.—Murphy, B., Bhattacharya, R., Mukherjee, P. disease. FASEB J. 33, 13098–13125 (2019). www.fasebj.org

Language: Английский

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Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(34)

Published: Aug. 16, 2021

Although most patients recover from acute COVID-19, some experience postacute sequelae of severe respiratory syndrome coronavirus 2 infection (PASC). One subgroup PASC is a called "long COVID-19," reminiscent myalgic encephalomyelitis/chronic fatigue (ME/CFS). ME/CFS debilitating condition, often triggered by viral and bacterial infections, leading to years-long symptoms including profound fatigue, postexertional malaise, unrefreshing sleep, cognitive deficits, orthostatic intolerance. Some are skeptical that either or long COVID-19 involves underlying biological abnormalities. However, in this review, we summarize the evidence people with have abnormalities redox imbalance, systemic inflammation neuroinflammation, an impaired ability generate adenosine triphosphate, general hypometabolic state. These phenomena not yet been well studied each them has reported other diseases as well, particularly neurological diseases. We also examine bidirectional relationship between inflammation, energy metabolic speculate what may be causing these Thus, understanding molecular underpinnings both lead development novel therapeutics.

Language: Английский

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Effects of hydrogen sulfide on mitochondrial function and cellular bioenergetics

Redox Biology, Journal Year: 2020, Volume and Issue: 38, P. 101772 - 101772

Published: Oct. 28, 2020

Hydrogen sulfide (H2S) was once considered to have only toxic properties, until it discovered be an endogenous signaling molecule. The effects of H2S are dose dependent, with lower concentrations being beneficial and higher concentrations, cytotoxic. This scenario is especially true for the on mitochondrial function, where gasotransmitter inhibit electron transport chain, stimulate bioenergetics in multiple ways. Here we review role function its cellular physiology.

Language: Английский

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Hydrogen sulfide is neuroprotective in Alzheimer’s disease by sulfhydrating GSK3β and inhibiting Tau hyperphosphorylation

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(4)

Published: Jan. 11, 2021

Alzheimer's disease (AD), the most common cause of dementia and neurodegeneration in elderly, is characterized by deterioration memory executive motor functions. Neuropathologic hallmarks AD include neurofibrillary tangles (NFTs), paired helical filaments, amyloid plaques. Mutations microtubule-associated protein Tau, a major component NFTs, its hyperphosphorylation AD. We have shown that signaling gaseous molecule hydrogen sulfide (H2S) dysregulated during aging. H2S signals via posttranslational modification termed sulfhydration/persulfidation, which participates diverse cellular processes. Here we show cystathionine γ-lyase (CSE), biosynthetic enzyme for H2S, binds wild type enhances catalytic activity. By contrast, CSE fails to bind Tau P301L, mutant present 3xTg-AD mouse model further depleted mice as well human brains, prevents sulfhydrating kinase, glycogen synthase kinase 3β (GSK3β). Finally, demonstrate sulfhydration diminished AD, while administering donor sodium GYY4137 (NaGYY) ameliorates cognitive deficits

Language: Английский

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Taking phototherapeutics from concept to clinical launch

Nature Reviews Chemistry, Journal Year: 2021, Volume and Issue: 5(11), P. 816 - 834

Published: Oct. 6, 2021

Language: Английский

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