Inactivation of ribonuclease and other enzymes by peroxidizing lipids and by malonaldehyde

Chio, K. S.; Tappel, Al L.

doi:10.1021/bi00835a020

Cited by 398 publications

(136 citation statements)

References 30 publications

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“…10). The increase occurs with an excitation maximum of 370 nm and an emission maximum of 450 nm, similar to the spectrum of lipofuscin or "age" pigments found in vivo, which are believed to be substituted I-amino-3-iminopropene structures, formed when auto-oxidized lipids react with protein (15,27,28).…”

Section: Mateirials and Methodssupporting

confidence: 63%

“…Studies on the oxidation of lipid-protein mixtures have demonstrated that one type of effect on the protein is the covalent binding of lipid oxidation products, some of which can result in fluorescent substituents, including crosslinks (15,27,28). This reaction also occurs in our system, as shown by the increase in protein fluorescence with increasing time of oxidation (Fig.…”

Section: Discussionmentioning

confidence: 71%

“…Although structural (7)(8)(9)(10)(11)(12)(13), spectrophotometric (9,13,14), and lipid compositional (8,11) changes in LDL have been observed upon oxidation, its polypeptide chain has not been characterized. Model studies with lipid-protein mixtures have shown that oxidized lipid can lead to major modification of protein components; such modifications include crosslinking (15), polypeptide scission (16), and loss of amino acids (17,18). It thus seems possible that some of the difficulties encountered in characterizing apo-B are associated with partial oxidation of LDL during purification and/or storage.…”

Section: Lutionsmentioning

confidence: 99%

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Oxygen-mediated heterogeneity of apo-low-density lipoprotein.

Schuh¹,

Fairclough²,

Haschemeyer³

1978

Proc. Natl. Acad. Sci. U.S.A.

245

121

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Mild oxidation of human serum low-density lipoprotein (LDL) converts the apoprotein from a nearly homogeneous component of high apparent molecular weight to a mixture of apparently lower mo ecular weight polypeptide components, as characterized by sodium dodecyl sulfate/ polyacrylamide gel electrophoresis. This protein alteration, which correlates temporally with increases in the formation of lipid oxidation products and in the fluorescence of the apoprotein, is markedly reduced when oxygen is excluded or when EDTA or the free-radical-scavenging antioxidants, butylated hydroxytoluene or propyl gallate, are added. The conversion thus appears to be due to a reaction between the protein moiety and auto-oxidizing lipid. The presence of the antibacterial agent sodium azide markedly accelerates the oxidation, suggesting that it should only be used with caution in lipid-containing solutions. Structural and functional characterization of serum lipoproteins has received attention because molecular or metabolic abnormalities associated with this class of molecules might be significant in the development of atherosclerosis (1). The lowdensity lipoprotein fraction (LDL) has been of particular interest because of its apparent role in atherogenesis. Such a role is indicated by a correlation between high serum levels of LDL and clinical atherosclerosis (2), as well as the accelerated atherosclerosis in patients who have an inherited abnormality in LDL catabolism (familial hypercholesterolemia) (3). LDL is catabolized after it is bound through its protein moiety (apo-B or apo-LDL) to a cell-surface receptor (4).Although characterization of the apoprotein of LDL has been difficult (5), studies on the lipid moiety appear to be less controversial. LDL contains a large proportion of unsaturated lipids (somewhat variable on diet) (6) and is unique among the serum lipoproteins in its susceptibility for undergoing auto-oxidation in vitro (7-9). This finding has led some authors to speculate that such auto-oxidation plays a role in atherogenesis (7,10,11). Although structural (7-13), spectrophotometric (9,13,14), and lipid compositional (8, 11) changes in LDL have been observed upon oxidation, its polypeptide chain has not been characterized. Model studies with lipid-protein mixtures have shown that oxidized lipid can lead to major modification of protein components; such modifications include crosslinking (15), polypeptide scission (16), and loss of amino acids (17, 18). It thus seems possible that some of the difficulties encountered in characterizing apo-B are associated with partial oxidation of LDL during purification and/or storage. The observation that plasma lipids from human subjects contain significant diene conjugation (an early manifestation of lipid auto-oxidation) suggests that oxidation of LDL can be initiated in vivo (19).We show here that mild oxidation of LDL in vitro results in altering the sodium dodecyl sulfate (NaDodSO4)-apoprotein electrophoretic pattern from a single major band of low mobility into nume...

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Section: Mateirials and Methodssupporting

confidence: 63%

Section: Discussionmentioning

confidence: 71%

Section: Lutionsmentioning

confidence: 99%

See 1 more Smart Citation

Oxygen-mediated heterogeneity of apo-low-density lipoprotein.

Schuh¹,

Fairclough²,

Haschemeyer³

1978

Proc. Natl. Acad. Sci. U.S.A.

245

121

View full text Add to dashboard Cite

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“…The fluorescence spectra observed in our experiment were identical to those observed on the reaction of the secondary products of oxidizing methyllinoleate and ribonuclease by Gamage et al 20 ) Chio and Tappel 21 ) reported similar but not identical spectra for arachidonate-inactivated ribonuclease, and attributed the fluorescence (emission max at 470 nm, excitation max at 395 nm) to Schiff base conjugate compounds produced from 8-amino groups and malonaldehyde. Thus, in the reaction system employed by Gamage et al 20 ) and us, some agents other than malonaldehyde appear to be involved in the fluorescence production.…”

Section: Discussionsupporting

confidence: 88%

Changes in Lysozyme due to Interaction with Vaporized Hexanal

Tashiro

Okitani

Utsunomiya

et al. 1985

Agricultural and Biological Chemistry

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“…End-products of lipid oxidation, such as malondialdehyde [67] and 4-hydroxynonenal (4-HNE) [68], are also inactivating agents, possibly via Schiff-base formation. Schiff bases are short-lived species formed by the reaction of carbonyl groups with amines, and can be formed, for example, during exposure of proteins to : (i) lipid-derived aldehydes [69], (ii) autoxidizing sugars (some of which form vicinal dicarbonyl compounds [70]), and (iii) amino acid-derived aldehydes, as mentioned earlier.…”

Section: Protein Damage By Radicals or Carbonyls Arising From Other Bmentioning

confidence: 99%

Biochemistry and pathology of radical-mediated protein oxidation

Dean

Stocker

et al. 1997

Biochemical Journal

1,548

982

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Radical-mediated damage to proteins may be initiated by electron leakage, metal-ion-dependent reactions and autoxidation of lipids and sugars. The consequent protein oxidation is O2-dependent, and involves several propagating radicals, notably alkoxyl radicals. Its products include several categories of reactive species, and a range of stable products whose chemistry is currently being elucidated. Among the reactive products, protein hydroperoxides can generate further radical fluxes on reaction with transition-metal ions; protein-bound reductants (notably dopa) can reduce transition-metal ions and thereby facilitate their reaction with hydroperoxides; and aldehydes may participate in Schiff-base formation and other reactions. Cells can detoxify some of the reactive species, e.g. by reducing protein hydroperoxides to unreactive hydroxides. Oxidized proteins are often functionally inactive and their unfolding is associated with enhanced susceptibility to proteinases. Thus cells can generally remove oxidized proteins by proteolysis. However, certain oxidized proteins are poorly handled by cells, and together with possible alterations in the rate of production of oxidized proteins, this may contribute to the observed accumulation and damaging actions of oxidized proteins during aging and in pathologies such as diabetes, atherosclerosis and neurodegenerative diseases. Protein oxidation may also sometimes play controlling roles in cellular remodelling and cell growth. Proteins are also key targets in defensive cytolysis and in inflammatory self-damage. The possibility of selective protection against protein oxidation (antioxidation) is raised.

show abstract

Inactivation of ribonuclease and other enzymes by peroxidizing lipids and by malonaldehyde

Cited by 398 publications

References 30 publications

Oxygen-mediated heterogeneity of apo-low-density lipoprotein.

Oxygen-mediated heterogeneity of apo-low-density lipoprotein.

Changes in Lysozyme due to Interaction with Vaporized Hexanal

Biochemistry and pathology of radical-mediated protein oxidation

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