Methionine oxidation of clusterin in Alzheimer's disease and its effect on clusterin's binding to beta-amyloid.

Clusterin is a secreted glycoprotein that participates in multiple physiological processes through its chaperon function. In Alzheimer's disease, the brain functions under an increased oxidative stress condition that causes an elevation of protein oxidation, resulting in enhanced pathology. Accordingly, it is important to determine the type of human brain cells that are mostly prone to methionine oxidation in Alzheimer's disease and specifically monitoring the methionine-oxidation levels of clusterin in human and mice brains and its effect on clusterin's function.

Seizures, ataxia and parvalbumin-expressing interneurons respond to selenium supply in Selenop-deficient mice.

Mice with constitutive disruption of the Selenop gene have been key to delineate the importance of selenoproteins in neurobiology. However, the phenotype of this mouse model is exquisitely dependent on selenium supply and timing of selenium supplementation. Combining biochemical, histological, and behavioral methods, we tested the hypothesis that parvalbumin-expressing interneurons in the primary somatosensory cortex and hippocampus depend on dietary selenium availability in Selenop mice.

Protective Effects against the Development of Alzheimer's Disease in an Animal Model through Active Immunization with Methionine-Sulfoxide Rich Protein Antigen.

The brain during Alzheimer's disease (AD) is under severe oxidative attack by reactive oxygen species that may lead to methionine oxidation. Oxidation of the sole methionine (Met35) of beta-amyloid (A), and possibly methionine residues of other extracellular proteins, may be one of the earliest events contributing to the toxicity of A and other proteins in vivo. In the current study, we immunized transgenic AD (APP/PS1) mice at 4 months of age with a recombinant methionine sulfoxide (MetO)-rich protein from (antigen).

Methionine sulfoxide and the methionine sulfoxide reductase system as modulators of signal transduction pathways: a review.

Methionine oxidation and reduction is a common phenomenon occurring in biological systems under both physiological and oxidative-stress conditions. The levels of methionine sulfoxide (MetO) are dependent on the redox status in the cell or organ, and they are usually elevated under oxidative-stress conditions, aging, inflammation, and oxidative-stress related diseases. MetO modification of proteins may alter their function or cause the accumulation of toxic proteins in the cell/organ.

Recent advances in iron homeostasis and regulation - a focus on epigenetic regulation and stroke.

Iron is an element with redox properties. It is active sites of many enzymes and plays an important role in various cellular and biological functions including ATP production and DNA synthesis. However, as a redox element, iron promotes free radical generation and lipid peroxidation, causing oxidative damage and cell death.

The Antioxidant Enzyme Methionine Sulfoxide Reductase A (MsrA) Interacts with Jab1/CSN5 and Regulates Its Function.

Methionine sulfoxide (MetO) is an oxidative posttranslational modification that primarily occurs under oxidative stress conditions, leading to alteration of protein structure and function. This modification is regulated by MetO reduction through the evolutionarily conserved methionine sulfoxide reductase (Msr) system. The Msr type A enzyme (MsrA) plays an important role as a cellular antioxidant and promotes cell survival.

Increased Levels of Protein-methionine Sulfoxide in Plasma Correlate with a Shift from a Mild Cognitive Impairment to an Alzheimer's Disease Stage.

: Sporadic Alzheimer's disease (AD) is an oxidative, stress-dependent neurodegenerative disease. We investigated whether the levels of protein-methionine sulfoxide (MetO) in plasma could be a possible marker for AD in individuals with mild cognitive impariment (MCI). : We evaluated blood samples from patients with AD or MCI, as well as from normal controls, testing their MetO levels and superoxide dismutase (SOD) specific activity.

Genetic regulation of longevity and age-associated diseases through the methionine sulfoxide reductase system.

Methionine sulfoxide reductase enzymes are a protective system against biological oxidative stress in aerobic organisms. Modifications to this antioxidant system have been shown to impact the lifespan of several model system organisms. In humans, methionine oxidation of critical proteins and deficiencies in the methionine sulfoxide reductase system have been linked to age-related diseases, including cancer and neurodegenerative disease.

The Functions of the Mammalian Methionine Sulfoxide Reductase System and Related Diseases.

This review article describes and discusses the current knowledge on the general role of the methionine sulfoxide reductase (MSR) system and the particular role of MSR type A (MSRA) in mammals. A powerful tool to investigate the contribution of MSRA to molecular processes within a mammalian system/organism is the knockout. The deficiency of MSRA in this mouse model provides hints and evidence for this enzyme function in health and disease.

Methionine sulfoxide reductase A (MsrA) mediates the ubiquitination of 14-3-3 protein isotypes in brain.

The methionine sulfoxide reductase (Msr) system is known for its function in reducing protein-methionine sulfoxide to methionine. Recently, we showed that one member of the Msr system, MsrA, is involved in the ubiquitination-like process in Archaea. Here, the mammalian MsrA is demonstrated to mediate the ubiquitination of the 14-3-3 zeta protein and to promote the binding of 14-3-3 proteins to alpha synuclein in brain.

Methionine Sulfoxide Reductase A Knockout Mice Show Progressive Hearing Loss and Sensitivity to Acoustic Trauma.

Methionine sulfoxide reductases (MsrA and MsrB) protect the biological activity of proteins from oxidative modifications to methionine residues and are important for protecting against the pathological effects of neurodegenerative diseases. In the current study, we characterized the auditory phenotype of the MsrA knockout mouse. Young MsrA knockout mice showed small high-frequency threshold elevations for auditory brainstem response and distortion product otoacoustic emission compared to those of wild-type mice, which progressively worsened in older MsrA knockout mice.

Methionine Sulfoxide Reductase A (MsrA) and Its Function in Ubiquitin-Like Protein Modification in .

Methionine sulfoxide reductase A (MsrA) is an antioxidant enzyme found in all domains of life that catalyzes the reduction of methionine--sulfoxide (MSO) to methionine in proteins and free amino acids. We demonstrate that archaeal MsrA has a ubiquitin-like (Ubl) protein modification activity that is distinct from its stereospecific reduction of MSO residues. MsrA catalyzes this Ubl modification activity, with the Ubl-activating E1 UbaA, in the presence of the mild oxidant dimethyl sulfoxide (DMSO) and in the absence of reductant.

Correction: Oxidation of Helix-3 Methionines Precedes the Formation of PK Resistant PrPSc.

[This corrects the article DOI: 10.1371/journal.ppat.

A Ratiometric Fluorescent Probe for Imaging of the Activity of Methionine Sulfoxide Reductase A in Cells.

Methionine sulfoxide reductase A (MsrA) is an enzyme involved in redox balance and signaling, and its aberrant activity is implicated in a number of diseases (for example, Alzheimer's disease and cancer). Since there is no simple small molecule tool to monitor MsrA activity in real time in vivo, we aimed at developing one. We have designed a BODIPY-based probe called (S)-Sulfox-1, which is equipped with a reactive sulfoxide moiety.

Manic symptom severity correlates with COMT activity in the striatum: A post-mortem study.

Objectives: The enzyme catechol-O-methyltransferase (COMT), which catalyses the degradation of dopamine and norepinephrine, is posited to participate in the pathophysiology of bipolar disorder (BD) and schizophrenia. In support of this notion, rich evidence has documented that the severity of various BD and schizophrenia symptoms is moderated by rs4680, a single nucleotide polymorphism of the COMT gene featuring a valine (Val)-to-methionine (Met) substitution that results in lower catalytic activity. Nevertheless, the specific relevance of COMT enzymatic activity in the pathophysiology of BD and schizophrenia dimensions remains elusive.

Methionine sulfoxide reductase A affects β-amyloid solubility and mitochondrial function in a mouse model of Alzheimer's disease.

Accumulation of oxidized proteins, and especially β-amyloid (Aβ), is thought to be one of the common causes of Alzheimer's disease (AD). The current studies determine the effect of an in vivo methionine sulfoxidation of Aβ through ablation of the methionine sulfoxide reductase A (MsrA) in a mouse model of AD, a mouse that overexpresses amyloid precursor protein (APP) and Aβ in neurons. Lack of MsrA fosters the formation of methionine sulfoxide in proteins, and thus its ablation in the AD-mouse model will increase the formation of methionine sulfoxide in Aβ.

Different Roles of N-Terminal and C-Terminal Domains in Calmodulin for Activation of Bacillus anthracis Edema Factor.

Bacillus anthracis adenylyl cyclase toxin edema factor (EF) is one component of the anthrax toxin and is essential for establishing anthrax disease. EF activation by the eukaryotic Ca2+-sensor calmodulin (CaM) leads to massive cAMP production resulting in edema. cAMP also inhibits the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, thus reducing production of reactive oxygen species (ROS) used for host defense in activated neutrophils and thereby facilitating bacterial growth.

Significance of four methionine sulfoxide reductases in Staphylococcus aureus.

Staphylococcus aureus is a major human pathogen and emergence of antibiotic resistance in clinical staphylococcal isolates raises concerns about our ability to control these infections. Cell wall-active antibiotics cause elevated synthesis of methionine sulfoxide reductases (Msrs: MsrA1 and MsrB) in S. aureus.

The enzymatic activities of brain catechol-O-methyltransferase (COMT) and methionine sulphoxide reductase are correlated in a COMT Val/Met allele-dependent fashion.

Aims: The enzyme catechol-O-methyltransferase (COMT) plays a primary role in the metabolism of catecholamine neurotransmitters and is implicated in the modulation of cognitive and emotional responses. The best characterized single nucleotide polymorphism (SNP) of the COMT gene consists of a valine (Val)-to-methionine (Met) substitution at codon 108/158. The Met-containing variant confers a marked reduction in COMT catalytic activity.

Membranous adenylyl cyclase 1 activation is regulated by oxidation of N- and C-terminal methionine residues in calmodulin.

Membranous adenylyl cyclase 1 (AC1) is associated with memory and learning. AC1 is activated by the eukaryotic Ca(2+)-sensor calmodulin (CaM), which contains nine methionine residues (Met) important for CaM-target interactions. During ageing, Met residues are oxidized to (S)- and (R)-methionine sulfoxide (MetSO) by reactive oxygen species arising from an age-related oxidative stress.

Hyperglycemia and redox status regulate RUNX2 DNA-binding and an angiogenic phenotype in endothelial cells.

Angiogenesis is regulated by hyperglycemic conditions, which can induce cellular stress responses, reactive oxygen species (ROS), and anti-oxidant defenses that modulate intracellular signaling to prevent oxidative damage. The RUNX2 DNA-binding transcription factor is activated by a glucose-mediated intracellular pathway, plays an important role in endothelial cell (EC) function and angiogenesis, and is a target of oxidative stress. RUNX2 DNA-binding and EC differentiation in response to glucose were conserved in ECs from different tissues and inhibited by hyperglycemia, which stimulated ROS production through the aldose reductase glucose-utilization pathway.

Methionine sulfoxide reductase regulates brain catechol-O-methyl transferase activity.

Catechol-O-methyl transferase (COMT) plays a key role in the degradation of brain dopamine (DA). Specifically, low COMT activity results in higher DA levels in the prefrontal cortex (PFC), thereby reducing the vulnerability for attentional and cognitive deficits in both psychotic and healthy individuals. COMT activity is markedly reduced by a non-synonymous single-nucleotide polymorphism (SNP) that generates a valine-to-methionine substitution on the residue 108/158, by means of as-yet incompletely understood post-translational mechanisms.

Detection and localization of methionine sulfoxide residues of specific proteins in brain tissue.

Methionine sulfoxide is a common posttranslational oxidative modification that can alter protein function. Vulnerability of specific proteins to methionine oxidation varies and depends on their structure. In the current study, detection of methionine sulfoxide in intact proteins is mediated by novel anti-methionine sulfoxide antibody that resulted in the identification of three major methionine sulfoxide-proteins in brain: bisphosphate aldolase A and C, α and β subunits of hemoglobin, and serum albumin.

Induction of methionine sulfoxide reductase activity by pergolide, pergolide sulfoxide, and S-adenosyl-methionine in neuronal cells.

The reduction of methionine sulfoxide in proteins is facilitated by the methionine sulfoxide reductase (Msr) system. The Msr reduction activity is important for protecting cells from oxidative stress related damages. Indeed, we have recently shown that treatment of cells with N-acetyl-methionine sulfoxide can increase Msr activity and protect neuronal cells from amyloid beta toxicity.