Biological aging does not lead to the accumulation of oxidized Cu,Zn-superoxide dismutase in the liver of F344 rats

Ghezzo-Schöneich, Elena; Esch, Steven Wynn; Sharov, Victor S.; Schöneich, Christian

doi:10.1016/s0891-5849(01)00473-7

Cited by 10 publications

(6 citation statements)

References 36 publications

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“…Although this protein does not have an iron-sulphur centre, it does bind bivalent cations : one of the essential requirements for metal-catalysed oxidation of proteins. Factors such as molecular conformation, rate of turnover and the relative abundance of amino acid residues susceptible to metal-catalysed oxidation have also been suggested to be involved in the selectivity of protein oxidative damage [40,41].…”

Section: Discussionmentioning

confidence: 99%

Selectivity of protein oxidative damage during aging in Drosophila melanogaster

DAS

Levine

Orr

et al. 2001

Biochemical Journal

102

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The purpose of the present study was to determine whether oxidation of various proteins during the aging process occurs selectively or randomly, and whether the same proteins are damaged in different species. Protein oxidative damage to the proteins, present in the matrix of mitochondria in the flight muscles of Drosophila melanogaster and manifested as carbonyl modifications, was detected immunochemically with anti-dinitrophenyl-group antibodies. Aconitase was found to be the only protein in the mitochondrial matrix that exhibited an age-associated increase in carbonylation. The accrual of oxidative damage was accompanied by an approx. 50% loss in aconitase activity. An increase in ambient temperature, which elevates the rate of metabolism and shortens the life span of flies, caused an elevation in the amount of aconitase carbonylation and an accelerated loss in its activity. Exposure to 100% ambient oxygen showed that aconitase was highly susceptible to undergo oxidative damage and loss of activity under oxidative stress. Administration of fluoroacetate, a competitive inhibitor of aconitase activity, resulted in a dose-dependent decrease in the life span of the flies. Results of the present study demonstrate that protein oxidative damage during aging is a selective phenomenon, and might constitute a mechanism by which oxidative stress causes age-associated losses in specific biochemical functions.

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Section: Discussionmentioning

confidence: 99%

Selectivity of protein oxidative damage during aging in Drosophila melanogaster

DAS

Levine

Orr

et al. 2001

Biochemical Journal

102

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“…Other factors, such as molecular conformation, rate of turnover and the relative abundance of amino acid residues susceptible to metal-catalysed oxidation, have also been suggested to be involved in the selectivity of protein carbonylation [28,29]. In addition, some proteins (e.g., enzymes of Krebs cycle and electron transport chain) may be carbonylated mainly because they are located near sites generating ROS.…”

Section: The Impact Of Carbonylation On Protein Functionmentioning

confidence: 99%

Protein carbonylation, cellular dysfunction, and disease progression

Dalle‐Donne

Aldini

Colombo

et al. 2006

Journal of Cellular and Molecular Medicine

728

545

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Carbonylation of proteins is an irreversible oxidative damage, often leading to a loss of protein function, which is considered a widespread indicator of severe oxidative damage and disease-derived protein dysfunction. Whereas moderately carbonylated proteins are degraded by the proteasomal system, heavily carbonylated proteins tend to form high-molecular-weight aggregates that are resistant to degradation and accumulate as damaged or unfolded proteins. Such aggregates of carbonylated proteins can inhibit proteasome activity. A large number of neurodegenerative diseases are directly associated with the accumulation of proteolysis-resistant aggregates of carbonylated proteins in tissues. Identification of specific carbonylated protein(s) functionally impaired and development of selective carbonyl blockers should lead to the definitive assessment of the causative, correlative or consequential role of protein carbonylation in disease onset and/or progression, possibly providing new therapeutic aproaches.

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“…To remove unbound metals, the SOD protein was then dialyzed several times against PBS (pH 7.4). The Cu/Zn content of native, demetalated, and remetalated bovine SOD1 was determined as previously described (49). Briefly, 10 μg SOD1 was mixed with 1 ml assay buffer containing 100 mM sodium borate (pH 7.8), 2% SDS, and 100 μM pyridylazoresorcinol (PAR).…”

Section: Demetalation Of Sod1mentioning

confidence: 99%