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At least 19 recordsLinked to original sources
PubMed2005

Post-translational protein modification as the substrate for long-lasting memory.

Prevailing models of memory identify mRNA translation as necessary for long-lasting information storage. However, there are enough instances of memory storage in the virtual absence of protein synthesis to prompt consideration of alternative models. A comprehensive review of the protein synthesis literature leads us to conclude that the translational mechanism is exclusively a permissive, replenishment step. Therefore, we propose that post-translational modification (PTM) of proteins already at the synapse is the crucial instructive mechanism underlying long-lasting memory. A novel feature of this model is that non-random spontaneous (or endogenous) brain activity operates as a regulated positive-feedback rehearsal mechanism, updating network configurations by fine-tuning the PTM state of previously modified proteins. Synapses participating in memory storage are therefore supple, a feature required for networks to alter complexity and update continuously. In analogy with codons for amino acids, a long-lasting memory is represented by a 'degenerate code' - a set of pseudo-redundant networks that can ensure its longevity.

Animals↗
PubMed2001

Post-translational protein modifications in antigen recognition and autoimmunity.

It is estimated that 50-90% of the proteins in the human body are post-translationally modified. In the proper context, these modifications are necessary for the biological functions of a vast array of proteins and the effector functions of the cells in which they reside. However, it is now clear that some post-translational modifications can create new self antigens (Ags) or even mask Ags normally recognized by the immune system. In either case, they profoundly affect the recognition of Ag by bone marrow-derived cells, as well as their effector functions. How do post-translational protein modifications affect the processing of foreign and self Ags and what is their role in the origin of autoimmune responses?

Animals↗
PubMed1989

Biosynthetic incorporation of [3H]ethanolamine into protein synthesis elongation factor 1 alpha reveals a new post-translational protein modification.

Biosynthetic incorporation of [3H]ethanolamine into proteins was assessed in the human erythroleukemia cell line K562. A single predominant labeled protein of about 50 kDa was observed following electrophoresis of cell extracts on polyacrylamide gels in the presence of sodium dodecyl sulfate. Subcellular fractionation showed this protein to distribute similarly to a 46-kDa [3H]ethanolamine-labeled protein reported previously (Tisdale, E. J., and Tartakoff, A. M. (1988) J. Biol. Chem. 263, 8244-8252). In particular, the protein was enriched in cytosolic and microsomal fractions relative to plasma membrane and thus did not appear to correspond to the class of proteins with glycoinositol phospholipid anchors, the only post-translational protein modification involving ethanolamine that had been described previously. Two-dimensional polyacrylamide gel analysis involving isoelectric focusing followed by electrophoresis in sodium dodecyl sulfate indicated that the protein was very basic, and nitrocellulose blots of one- and two-dimensional gels subjected to 3H autoradiography and immunostaining with antisera to purified rabbit elongation factor (EF) 1 alpha revealed that the protein was EF-1 alpha. Copurification of rabbit EF-1 alpha and the [3H]ethanolamine-labeled protein from K562 cells further supported this identification. Analysis of tryptic fragments produced from the copurified proteins by reverse-phase high pressure liquid chromatography showed two radiolabeled peptides. Amino acid analysis demonstrated 1 residue of ethanolamine in each peptide, and peptide sequencing revealed that the ethanolamine-containing component(s) was attached to Glu301 and Glu374 in the EF-1 alpha protein sequence deduced from a human EF-1 alpha cDNA. These data confirm a new class of post-translational protein modifications involving ethanolamine.

Animals↗
PubMed2005

Effect of arginine deficiency on arginine-dependent post-translational protein modifications in mice.

Transgenic mice that overexpress arginase-I in their small-intestinal enterocytes suffer from a pronounced, but selective decrease in circulating arginine levels during the suckling period, resulting in impaired growth and development of hair, muscle and immune system. In the present study, we tested the hypothesis that the arginine-deficiency phenotype is caused by arginine-specific post-translational modifications, namely, an increase in the degree of mono-ADP-ribosylation of proteins because of reduced competition by free arginine residues and/or an increase in protein-tyrosine nitration because of an increased O2- production by NO synthases in the presence of limiting amounts of arginine. Arginine ADP-ribosylation and tyrosine nitration of proteins in the affected organs were assayed by Western blot analysis, using specific anti-ADP-ribosylarginine and protein-nitrotyrosine antisera. The composition of the group of proteins that were preferentially arginine ADP-ribosylated or tyrosine-nitrated in the respective organs was strikingly similar. Arginine-deficient mice differed from their controls in a reduced ADP-ribosylation of a 130 kDa and a 65 kDa protein in skin and an increased protein nitration of an 83 kDa protein in bone marrow and a 250 kDa protein in spleen. Since only 20 % of the visualised proteins were differentially modified in a subset of the affected organs, our findings appear to rule out these prominent arginine-dependent post-translational protein modifications as mediators of the characteristic phenotype of severely arginine-deficient mice.

Adenosine Diphosphate↗
PubMed2007

Post-translational protein modifications in type 1 diabetes: a role for the repair enzyme protein-L-isoaspartate (D-aspartate) O-methyltransferase?

AIMS/HYPOTHESIS: Post-translational modifications, such as isomerisation of native proteins, may create new antigenic epitopes and play a role in the development of the autoimmune response. Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PIMT), encoded by the gene PCMT1, is an enzyme that recognises and repairs isomerised Asn and Asp residues in proteins. The aim of this study was to assess the role of PIMT in the development of type 1 diabetes. MATERIALS AND METHODS: Immunohistochemical analysis of 59 normal human tissues was performed with a monoclonal PIMT antibody. CGP3466B, which induces expression of Pcmt1, was tested on MIN6 and INS1 cells, to assess its effect on Pcmt1 mRNA and PIMT levels (RT-PCR and western blot) and apoptosis. Forty-five diabetes-prone BioBreeding (BB) Ottawa Karlsburg (OK) rats were randomised to receive 0, 14 or 500 microg/kg (denoted as the control, low-dose and high-dose group, respectively) of CGP3466B from week 5 to week 20. RESULTS: A high level of PIMT protein was detected in beta cells. CGP3466B induced a two- to threefold increase in Pcmt1 mRNA levels and reduced apoptosis by 10% in MIN6 cells. No significant effect was seen on cytokine-induced apoptosis or PIMT protein levels in INS1 cells. The onset of diabetes in the BB/OK rats was significantly delayed (85.6+/-9.0 vs 84.3+/-6.8 vs 106.6+/-13.5 days, respectively; p<0.01 for high-dose vs low-dose and control groups), the severity of the disease was reduced (glucose 22.2+/-3.2 vs 16.9+/-2.6 vs 15.8+/-2.7 mmol; p<0.01 for high- and low-dose groups vs control group) and residual beta cells were more frequently identified (43% vs 71% vs 86%; p<0.05 for high-dose vs control group) in the treated animals. CONCLUSIONS/INTERPRETATION: The results support a role for post-translational modifications and PIMT in the development of type 1 diabetes in the diabetes-prone BB rat, and perhaps also in humans.

Animals↗
PubMed1983

Incorporation of 3H-amino acids into proteins in a partially purified fraction of axoplasm: evidence for transfer RNA-mediated, post-translational protein modification in squid giant axons.

Transfer RNA (tRNA) has been demonstrated to be present in axons of both invertebrates and the higher vertebrates, but nothing is known of its role in the metabolism of the axon. The present experiments were performed to determine whether tRNA functions in axons as a participant in post-translational protein modification of endogenous proteins. RNA was extracted from the axoplasm of squid giant axons and incubated with a variety of 3H-amino acids, aminoacyl-tRNA synthetases (obtained from squid optic lobe), and an appropriate reaction mixture. All of the amino acids tested were bound to an RNA fraction, but this reaction did not occur when samples were incubated in the presence of ribonuclease or in the absence of axoplasmic RNA. When radioactive RNA was chromatographed by polyacrylamide gel electrophoresis, the radioactivity comigrated with known tRNA markers, suggesting the presence of 3H-aminoacylated tRNA. Aminoacylation of RNA could also be demonstrated by incubating fresh axoplasm with labeled amino acids and a reaction mixture, minus exogenous aminoacyl-tRNA synthetases. These findings indicate the presence in axoplasm of a variety of species of aminoacyl-tRNAs as well as their corresponding synthetase enzymes. In the latter experiment no radioactivity was found associated with the protein fraction. This was also the finding when 3H-aminoacylated tRNA was either injected directly into the axon or incubated with extruded axoplasm. Thus, under the conditions described above, there is no evidence of transfer of amino acids from tRNA to proteins. In other experiments, axoplasm was pooled to a volume of 50 to 100 microliters, homogenized gently, and centrifuged at 150,000 X g for 1 hr. Some of the high speed supernatant was incubated with labeled amino acids and an appropriate reaction mixture, and the remainder was passed through an S-200 Sephacryl column before incubation with the same reaction mixture. There was no incorporation of amino acids into protein in the high speed supernatant fraction. However, in the S-200 purified fraction 3H-labeled Arg, Lys, Tyr, Leu, and Asp were all incorporated into proteins in amounts of 44, 30, 7, 5 and 3.5 times heat-inactivated controls. The reaction is not inhibited by Ca2+ or Ca2+-activated proteases, but appears to be dependent on the presence of tRNA. The addition of amino acids to protein is not protein synthesis since the reactions occurred in a partially purified fraction of the 150,000 X g supernatant, a fraction devoid of ribosomes and free amino acids.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗
PubMed2000

Non-oxidative modification of lens crystallins by kynurenine: a novel post-translational protein modification with possible relevance to ageing and cataract.

In humans, the crystallin proteins of the ocular lens become yellow-coloured and fluorescent with ageing. With the development of senile nuclear cataract, the crystallins become brown and additional fluorophores are formed. The mechanism underlying crystallin colouration is not known but may involve interaction with kynurenine-derived UV filter compounds. We have recently identified a sulphur-linked glutathionyl-3-hydroxykynurenine glucoside adduct in the lens and speculated that kynurenine may also form adducts with GSH and possibly with nucleophilic amino acids of the crystallins (e.g. Cys). Here we show that kynurenine modifies calf lens crystallins non-oxidatively to yield coloured (365 nm absorbing), fluorescent (Ex 380 nm/Em 450-490 nm) protein adducts. Carboxymethylation and succinylation of crystallins inhibited kynurenine-mediated modification by approx. 90%, suggesting that Cys, Lys and possibly His residues may be involved. This was confirmed by showing that kynurenine formed adducts with GSH as well as with poly-His and poly-Lys. NMR studies revealed that the novel poly-Lys-kynurenine covalent linkage was via the epsilon-amino group of the Lys side chain and the betaC of the kynurenine side chain. Analysis of tryptic peptides of kynurenine-modified crystallins revealed that all of the coloured peptides contained either His, Cys or an internal Lys residue. We propose a novel mechanism of kynurenine-mediated crystallin modification which does not require UV light or oxidative conditions as catalysts. Rather, we suggest that the side chain of kynurenine-derived lens UV filters becomes deaminated to yield an alpha,beta-unsaturated carbonyl which is highly susceptible to attack by nucleophilic amino acid residues of the crystallins. The inability of the lens fibre cells to metabolise their constituent proteins results in the accumulation of coloured/fluorescent crystallins with age.

Aging↗
PubMed2006

Proteomics of acute myeloid leukaemia: Cytogenetic risk groups differ specifically in their proteome, interactome and post-translational protein modifications.

Acute myeloid leukaemia (AML) is characterized by specific cytogenetic aberrations that are strong determinants of prognostic outcome and therapeutic response. Because the pathological outcome of AML patients with cytogenetic abnormalities differs considerably, we hypothesized that their proteome may also differ specifically in their expression pattern, protein interaction pathways and post-translational modifications (PTM). We performed this study using 42 AML patients diagnosed for various cytogenetic abnormalities based on two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MS) and MSMS tandem MS. We could identify significant differences in the proteome and PTM of peptides, later confirmed by other methods, between cytogenetic groups. The interactome analysis based on computational bioinformatics reveals major regulating networks: MAPK8 and MYC for complex aberrant karyotype, TP53 for t(8;21), TP53-MYC-PRKAC for 11q23 and JUN and MYC for Inv(16). Further, we analysed 42 MS spectra representative of hnRNPH1, calreticulin and hnRNPA2/B1 in a peak explorer, which reveals a cytogenetic-specific PTM of beta-O-linked N-acetyl glucosamine (O-GlcNAc) of hnRNPH1 in AML patients with 11q23 translocation, an acetylation of calreticulin in t(8;21) translocation and methylation of hnRNPA2/B1 in patients with translocations of t(8;21) and inv(16). This report may lead to a new thinking about AML pathogenesis, as differences at PTM level could be used to distinguish different subtypes of AML.

Cell Shape↗
PubMed2002

Primary and secondary metabolism, and post-translational protein modifications, as portrayed by proteomic analysis of Streptomyces coelicolor.

The newly sequenced genome of Streptomyces coelicolor is estimated to encode 7825 theoretical proteins. We have mapped approximately 10% of the theoretical proteome experimentally using two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. Products from 770 different genes were identified, and the types of proteins represented are discussed in terms of their annotated functional classes. An average of 1.2 proteins per gene was observed, indicating extensive post-translational regulation. Examples of modification by N-acetylation, adenylylation and proteolytic processing were characterized using mass spectrometry. Proteins from both primary and certain secondary metabolic pathways are strongly represented on the map, and a number of these enzymes were identified at more than one two-dimensional gel location. Post-translational modification mechanisms may therefore play a significant role in the regulation of these pathways. Unexpectedly, one of the enzymes for synthesis of the actinorhodin polyketide antibiotic appears to be located outside the cytoplasmic compartment, within the cell wall matrix. Of 20 gene clusters encoding enzymes characteristic of secondary metabolism, eight are represented on the proteome map, including three that specify the production of novel metabolites. This information will be valuable in the characterization of the new metabolites.

Acetylation↗
PubMed1982

Effects of hydrocortisone and aspirin on protein synthesis and post-translational protein modification in cultured cells.

Arginyl-tRNA transferase is suggested to function as a post-translational modifier of proteins through the addition of arginine to the NH2-terminus of specific acceptor proteins. Both hydrocortisone and aspirin produced an age-dependent stimulation of protein synthesis in normal human fibroblasts (IMR90), while producing an inhibition of protein synthesis in SV40 virus-transformed IMR90 cells. The effect of aspirin was confined primarily to the cytoplasmic compartment, whereas hydrocortisone produced its effect at both cytoplasmic and nuclear levels. Neither hydrocortisone nor aspirin had a direct effect on arginyl-tRNA transferase activity in vitro; however, hydrocortisone resulted in a marked increase in the availability of chromosomal proteins subject to modification by arginyl-tRNA transferase. This stimulatory effect was attenuated by increasing culture age. The modified chromosomal proteins were found to be dissociated from native chromatin, suggesting that arginylation either triggered their release or prevented reassociation with chromatin thereafter. Hydrocortisone produced a moderate decrease in the availability of chromosomal proteins for arginylation in SV40 virus-transformed cells, and this effect was not modulated by aging phenomena.

Acyltransferases↗
PubMed2004

Techniques for studying protein heterogeneity and post-translational modifications.

Proteins often undergo several post-translational modification steps in parallel to protein folding. These modifications can be transient or of a more permanent nature. Most modifications are, however, susceptible to alteration during the lifespan of proteins. Post-translational modifications thus generate variability in proteins that are far beyond that provided by the genetic code. Co- and post-translational modifications can convert the 20 specific codon-encoded amino acids into more than 100 variant amino acids with new properties. These, and a number of other modifications, can considerably increase the information content and functional repertoire of proteins, thus making their analysis of paramount importance for diagnostic and basic research purposes. Various methods used in proteomics, such as 2D gel electrophoresis, 2D liquid chromatography, mass spectrometry, affinity-based analytical methods, interaction analyses, ligand blotting techniques, protein crystallography and structure-function predictions, are all applicable for the analysis of these numerous secondary modifications. In this review, examples of some of these techniques in studying the heterogeneity of proteins are highlighted. In the future, these methods will become increasingly useful in biomarker searches and in clinical diagnostics.

Humans↗
PubMed1983

Myristyl amino-terminal acylation of murine retrovirus proteins: an unusual post-translational proteins modification.

The primary structure of the NH(2)-terminal region of the gag gene encoded internal membrane-associated protein p15 has been determined for both Rauscher and Moloney murine leukemia viruses. Peptides generated by endopeptidases and purified by HPLC were subjected to semi-automated Edman degradation. Dipeptides obtained with dipeptidyl carboxypeptidase were identified by gas chromatography-mass spectrometry. The amino acid sequence of the first 16-residue segment of Rauscher p15 is identical to the sequence of Moloney p15 except for a single amino acid substitution (Gly-->Asp) at position 13. Both proteins were found to have an acylated NH(2) terminus. By mass spectroscopy, myristic acid [CH(3)(CH(2))(12)COOH] was found to be bound through an amide linkage to the NH(2)-terminal glycyl residue in both p15s. The results of liquid chromatography show that the NH(2)-terminal myristyl group greatly contributes to the strong binding of these modified proteins and peptides to hydrophobic surfaces. Because p15 is known to be derived from the NH(2)-terminal region of a precursor polyprotein Pr65(gag) by proteolytic cleavage in the assembled virus, it is suggested that myristylation in vivo takes place during the biosynthesis of Pr65(gag). Preliminary data indicate that such modification of gag precursor polyproteins may be common to mammalian retroviruses. The role of NH(2)-terminal myristyl acylation of Pr65(gag) in virus assembly and the possibility of similar NH(2)-terminal modifications of gag-related fusion proteins of transforming viruses are discussed.

Acylation↗
PubMed1988

Post-translational protein modification in the endoplasmic reticulum. Demonstration of fatty acylase and deoxymannojirimycin-sensitive alpha-mannosidase activities.

We have previously described a hybrid protein, GHHA, that contains a fragment of the influenza hemagglutinin joined to the C terminus of a nearly complete rat growth hormone (Rizzolo, L.J., Finidori, J., Gonzalez, A., Arpin, M., Ivanov, I.E., Adesnik, M., and Sabatini, D.D. (1985) J. Cell Biol. 101, 1351-1362). GHHA was transported from the rough endoplasmic reticulum (ER) to a smooth cisterna, continuous with the rough ER, but proximal to the Golgi apparatus. We have now labeled GHHA with [3H]palmitate, demonstrating that fatty acylation can occur in the ER. As expected for a thioester linkage, the label was released from GHHA by hydroxylamine and identified as palmitic acid by thin-layer chromatography. In a second study, we analyzed the structure of the N-linked carbohydrate chain of GHHA. The N-linked oligosaccharides, all high-mannose type, were released by endoglycosidase H and size-fractionated by high pressure liquid chromatography. The predominant structures were Glc1Man8GlcNAc and Man8GlcNAc, indicating that only 2 or 3 glucose and 1 mannose residues were removed from the original Glc3Man9GlcNAc2. Determination of the structure by acetolysis fragmentation indicated that a single Man8GlcNAc isomer was formed by a deoxymannojirimycin-sensitive alpha-mannosidase. This contrasts with a previously characterized ER alpha-mannosidase (Bischoff, J., Liscum, L., and Kornfeld, R. (1986) J. Biol. Chem. 261, 4766-4774) that generates the same isomer, but is deoxymannojirimycin-resistant. These data suggest the possibility that different enzymes are partitioned within the ER.

1-Deoxynojirimycin↗
PubMed2007

Oxidative-nitrosative stress and post-translational protein modifications: implications to lung structure-function relations. Arginase modulates NF-kappaB activity via a nitric oxide-dependent mechanism.

NF-kappaB is a versatile transcription factor that regulates a wide array of processes, including inflammation and survival, and plays a critical role in the etiology of inflammatory lung diseases. Nitric oxide (NO) has been suggested to play an antiinflammatory role through S-nitrosation of components of NF-kappaB pathway. NO production can be modulated by changing the availability of its substrate, L-arginine. Arginases compete with NO synthases (NOSs) for their common substrate, L-arginine, and thereby have the potential to alter the signaling function of NO. The goal of the present study was to determine the impact of arginase manipulation on NO, and subsequent effects on NF-kappaB activation, in lung epithelial cells. Our results demonstrate that reduction of arginase activity enhanced cellular content of NO and S-nitrosated proteins, and resulted in decreases in TNF-alpha- or LPS-stimulated NF-kappaB DNA binding and transcriptional activity, in association with enhanced S-nitrosation of p50. The effects of arginase inhibition on NF-kappaB were reversed by the generic NOS inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), suggesting a causal role for NO in the attenuation of NF-kappaB induced by arginase suppression. Conversely, overexpression of arginase I decreased cellular S-nitrosothiol content and enhanced IkappaB kinase activity and NF-kappaB DNA binding, and decreased S-nitrosation of p50. Collectively, our data point to a regulatory mechanism wherein NF-kappaB is controlled through arginase-dependent regulation of NO levels, which may impact on chronic inflammatory diseases that are accompanied by NF-kappaB activation and upregulation of arginases.

Animals↗
PubMed1991

Post-translational protein modification and expression of ankyrin-binding site(s) in GP85 (Pgp-1/CD44) and its biosynthetic precursors during T-lymphoma membrane biosynthesis.

In this study, we have investigated the biosynthesis and processing of GP85 (Pgp-1/CD44), a lymphoma transmembrane glycoprotein known to contain ankyrin-binding site(s). Using a standard pulse-chase protocol, we have detected a 52-kDa polypeptide precursor (p52) within the first 5 min of pulse labeling which contains a high mannose-type N-linked oligosaccharide chains. The conversion of p52 to GP85 requires further glycosylation (both complex type N-linked and O-linked) which takes place in the Golgi complex within 10-20 min after p52 is synthesized. GP85 is then incorporated into the plasma membrane where its turnover rate is relatively slow, a t1/2 of approximately 8 h. Following tunicamycin treatment, we have detected two other precursor proteins: p42 which is unglycosylated and p58 which is O-glycosylated. p42 appears to be an immediate precursor of p52 because p52 is converted to p42 upon deglycosylation. Therefore, the biosynthesis of GP85 appears to occur in the following sequence: p42 in equilibrium to p52 in equilibrium to GP85. Further analysis reveals that all of the GP85 precursors (i.e. p42, p52, and p58) contain ankyrin-binding site(s). Chemical composition analysis of GP85 indicates that this molecule contains approximately 3 N-linked and 4-5 O-linked oligosaccharide chains. Although neither N-glycosylation nor O-glycosylation appears to play an important role in the formation of ankyrin-binding site(s), O-glycosylation (and to a lesser extent N-glycosylation) of GP85 is required for T-lymphoma cell surface interaction with both collagen and hyaluronic acid. These findings suggest that GP85 (Pgp-1/CD44) and its biosynthetic precursors play a pivotal role in regulating adhesion functions such as lymphocyte homing and binding to the extracellular matrix.

Animals↗
PubMedDate not supplied

Relationship between enzymatic activity loss and post-translational protein modification in aging.

During aging, there is a decrease in the activity of many enzymes. The mechanism causing the loss of activity is still not well understood in most cases. We have studied the decrease in the activities of the malic, 6-phosphogluconate dehydrogenase and superoxide dismutase enzymes. The old malic enzyme is about 36% less active than the young enzyme and the old 6-phosphogluconic dehydrogenase enzyme is about 26% less active than the young enzyme. In this paper, some chemical properties of these enzymes are studied. Diethyl pyrocarbonate measurements indicate that the old malic enzyme has 1 histidine residue less than the young malic enzyme. Moreover, the treatment of the young malic enzyme with ascorbate for 15 min produces the loss of 36% of enzymatic activity and the loss of 1.2 histidine residues. 2,4,6-trinitrobenzenesulfonic acid measurements indicate that the old 6-phosphogluconate dehydrogenase enzyme has 11 lysine residues less than the young 6-phosphogluconate dehydrogenase enzyme. The proteolysis with trypsin produces more peptides in the young 6-phosphogluconate dehydrogenase enzyme than in the old one. However, similar numbers of peptides were produced when endoproteinase Arg-C was used in both enzymes, young and old 6-phosphogluconate dehydrogenase. Moreover, the treatment of young 6-phosphogluconate dehydrogenase enzyme with ascorbate for 15 min produces the loss of 8 lysine residues. These results suggest that during aging the modification of histidine residue could be involved in the loss of malic enzyme activity, and the modification of lysine residues could be involved in the loss of 6-phosphogluconate dehydrogenase activity. These results could also suggest that the modification of histidine and lysine residues during aging could be produced by oxidation. This could be a general process in aging, with an increase in the oxidation of many proteins. The relevance of this process in the aging effects must be related to the kind of proteins that are susceptible of oxidation and that this oxidation affects their enzymatic or biological function. We have also studied other enzymes one of which is the superoxide dismutase enzyme involved in the protection against oxidative damage. Our results are similar to those described for malic enzyme. In the latter case, the failure to measure one of the histidines in the Cu/Zn SOD is due to a chemical modification, probably caused by oxidation of the residue.

Journal Article↗