Potential mechanism of emphysema: alpha 1-proteinase inhibitor recovered from lungs of cigarette smokers contains oxidized methionine and has decreased elastase inhibitory capacity.

Carp, H.; Miller, Frederick J.; Hoidal, John R.; Janoff, Aaron

doi:10.1073/pnas.79.6.2041

Cited by 314 publications

(157 citation statements)

References 36 publications

Supporting

Mentioning

142

Contrasting

Unclassified

Order By: Relevance

“…Methionine dietary supplementation also increases iron and lipid peroxidation in rat liver (Mori and Hirayama 2004). Oxidation of methionine residues generates methionine sulfoxide in proteins, which deprives them of their function as methyl donors and may lead to loss of their biological activity (Carp et al 1982;Ciorba et al 1997). However, this modification can be repaired by methionine sulfoxide reductase in a thioredoxin-dependent reaction.…”

Section: Discussionmentioning

confidence: 99%

Protein and lipid oxidative damage and complex I content are lower in the brain of budgerigar and canaries than in mice. Relation to aging rate

Pamplona

Portero‐Otín

Sanz

et al. 2005

AGE

View full text Add to dashboard Cite

What are the mechanisms determining the rate of animal aging? Of the two major classes of endothermic animals, bird species are strikingly long-lived compared to mammals of similar body size and metabolic rate. Thus, they are ideal models to identify longevity-related characteristics not linked to body size or low metabolic rates. Since oxidative stress seems to be related to the basic aging process, we measured specific markers of different kinds of oxidative damage to proteins, like glutamic and aminoadipic semialdehydes (GSA and AASA, specific protein carbonyls), N(-(carboxyethyl)lysine (CEL), N(-(carboxymethyl)lysine (CML), and N(-(malondialdehyde)lysine (MDAL), as well as mitochondrial Complex I content and amino acid and membrane fatty acyl composition, in the brain of short-lived mice (maximum life span [MLSP] 3.5 years) compared with those of long-lived budgerigar Fparakeets_ (MLSP, 21 years) and canaries (MLSP, 24 years). The brains of both bird species had significantly lower levels of compounds formed as a result of oxidative (GSA and AASA), glycoxidative (CEL and CML), and lipoxidative (CML and MDAL) protein modifications, as well as a lower levels of mitochondrial complex I protein. Although it is known that fatty acid unsaturation is lower in many tissues of long-lived compared to short-lived mammals, this is not true in the particular case of brain. In agreement with this, we also found that the brain tissue of bugerigars and canaries contains no fewer double bonds than that of mice. Amino acid composition analyses revealed that bird proteins have a significantly lower content of His, Leu and Phe, as well as, interestingly, of methionine, whereas Asp, Glu, Ala, Val, and Lys contents were higher than in the mammals. These results, together with those previously described in other tissues of pigeons (MLSP, 35 years) compared to rats (MLSP, 4 years), indicate that oxidative damage to proteins, lipids and mitochondrial DNA are lower in birds (very long-lived species) than in short-lived mammals of similar body size. The lower degree of oxidative modification of bird brain proteins was not due to decreases in the target amino acids (lysine for CEL, CML, MDAL, and AASA; and arg and pro for GSA), since these were present in bird brain proteins at higher or similar levels than in those of mice. These results are consistent with the possibility that decreases in oxidative protein modification are caused at least in part by the low rate of mitochondrial oxygen radical generation in these birds, as in all long-lived homeothermic vertebrates investigated so far.

show abstract

Section: Discussionmentioning

confidence: 99%

Protein and lipid oxidative damage and complex I content are lower in the brain of budgerigar and canaries than in mice. Relation to aging rate

Pamplona

Portero‐Otín

Sanz

et al. 2005

AGE

View full text Add to dashboard Cite

show abstract

“…Oxidation of Met to methionine sulfoxide occurs in association with oxidative stress and aging (169,170). Such oxidation affects biological activity as shown by loss of ␣ 1 -antitrypsin inhibitor activity upon Met oxidation (22). Two types of methionine sulfoxide reductases act on the structurally distinct S-and R-sulfoxides (65,89,196); methionine sulfoxide reductases activities are dependent on thioredoxins (Trx) (196) and have been associated with longevity (123,130,147,152).…”

Section: The Redox Hypothesismentioning

confidence: 99%

Radical-free biology of oxidative stress

Jones¹

2008

American Journal of Physiology-Cell Physiology

1,032

839

View full text Add to dashboard Cite

Free radical-induced macromolecular damage has been studied extensively as a mechanism of oxidative stress, but large-scale intervention trials with free radical scavenging antioxidant supplements show little benefit in humans. The present review summarizes data supporting a complementary hypothesis for oxidative stress in disease that can occur without free radicals. This hypothesis, which is termed the "redox hypothesis," is that oxidative stress occurs as a consequence of disruption of thiol redox circuits, which normally function in cell signaling and physiological regulation. The redox states of thiol systems are sensitive to twoelectron oxidants and controlled by the thioredoxins (Trx), glutathione (GSH), and cysteine (Cys). Trx and GSH systems are maintained under stable, but nonequilibrium conditions, due to a continuous oxidation of cell thiols at a rate of about 0.5% of the total thiol pool per minute. Redox-sensitive thiols are critical for signal transduction (e.g., H-Ras, PTP-1B), transcription factor binding to DNA (e.g., Nrf-2, nuclear factor-B), receptor activation (e.g., ␣IIb␤3 integrin in platelet activation), and other processes. Nonradical oxidants, including peroxides, aldehydes, quinones, and epoxides, are generated enzymatically from both endogenous and exogenous precursors and do not require free radicals as intermediates to oxidize or modify these thiols. Because of the nonequilibrium conditions in the thiol pathways, aberrant generation of nonradical oxidants at rates comparable to normal oxidation may be sufficient to disrupt function. Considerable opportunity exists to elucidate specific thiol control pathways and develop interventional strategies to restore normal redox control and protect against oxidative stress in aging and age-related disease.thioredoxin; glutathione; cysteine; hydrogen peroxide; redox signaling; protein thiol ONE OF THE GREAT REDOX BIOLOGISTS of the past century, Howard S. Mason, professed that to advance science, a scientist must interpret observations at the limit of their meaning. The present review of the redox biology of thiol systems addresses the possibility that disruption of the function and homeostasis of thiol systems is the most central feature of oxidative stress that contributes to mechanisms of aging and age-related disease. I have termed this the "redox hypothesis" to facilitate distinction from free radical hypotheses.Many proteins contain redox-sensitive thiols, and reactions of thiol systems occur largely by nonradical two-electron transfers. Accumulating data show that central thiol-disulfide couples are maintained under nonequilibrium conditions in biological systems. This presents a condition wherein changes in abundance and distribution of redox catalysts and changes in rates of generation of relevant oxidants (e.g., peroxides) and precursors for NADPH supply can account for pathological effects of oxidative stress through altered functions of enzymes, receptors, transporters, transcription factors, and structural elements, without free ra...

show abstract

“…Two lines of evidence can be cited to support a role for smoke-borne radicals in smoking-induced pathology. Firstly, the evidence is becoming increasingly strong that free radicals are involved in many of the chronic diseases that are associated with smoking (23)(24)(25); in particular, radicals appear involved in emphysema (26) and chemical carcinogenesis (27)(28)(29)(30)(31). Secondly, the concentrations of radicals in smoke are so high (compared, for example, with smog) that radical-mediated reaction pathways appear certain to result from the exposure of tissue to smoke.…”

Section: Introductionmentioning

confidence: 99%

Free-Radical Chemistry of Cigarette Smoke and Its Toxicological Implications

Church¹,

Pryor²

1985

Environmental Health Perspectives

330

297

View full text Add to dashboard Cite

Cigarette smoke contains two very different populations of free radicals, one in the tar and one in the gas phase. The tar phase contains several relatively stable free radicals; we have identified the principal radical as a quinone/hydroquinone (Q/QH2) complex held in the tarry matrix. We suggest that this Q/QH2 polymer is an active redox system that is capable of reducing molecular oxygen to produce superoxide, eventually leading to hydrogen peroxide and hydroxyl radicals. In addition, we have shown that the principal radical in tar reacts with DNA in vitro, possibly by covalent binding.The gas phase of cigarette smoke contains small oxygen-and carbon-centered radicals that are much more reactive than are the tar-phase radicals. These gas-phase radicals do not arise in the flame, but rather are produced in a steady state by the oxidation of NO to NO2, which then reacts with reactive species in smoke such as isoprene. We suggest that these radicals and the metastable products derived from these radical reactions may be responsible for the inactivation of a,-proteinase inhibitor by fresh smoke.Cigarette smoke oxidizes thiols to disulfides; we suggest the active oxidants are NO and NO2. The effects of smoke on lipid peroxidation are complex, and this is discussed. We also discuss the toxicological implications for the radicals in smoke in terms of a number of radical-mediated disease processes, including emphysema and cancer.

show abstract

Potential mechanism of emphysema: alpha 1-proteinase inhibitor recovered from lungs of cigarette smokers contains oxidized methionine and has decreased elastase inhibitory capacity.

Abstract: The elastase inhibitory capacity per mg of atproteinase inhibitor (aPI)

Cited by 314 publications

References 36 publications

Protein and lipid oxidative damage and complex I content are lower in the brain of budgerigar and canaries than in mice. Relation to aging rate

Protein and lipid oxidative damage and complex I content are lower in the brain of budgerigar and canaries than in mice. Relation to aging rate

Radical-free biology of oxidative stress

Free-Radical Chemistry of Cigarette Smoke and Its Toxicological Implications

Contact Info

Product

Resources

About