Signaling by 4-hydroxy-2-nonenal: Exposure protocols, target selectivity and degradation.

4-hydroxy-2-nonenal (HNE), a major non-saturated aldehyde product of lipid peroxidation, has been extensively studied as a signaling messenger. In these studies a wide range of HNE concentrations have been used, ranging from the unstressed plasma concentration to far beyond what would be found in actual pathophysiological condition. In addition, accumulating evidence suggest that signaling protein modification by HNE is specific with only those proteins with cysteine, histidine, and lysine residues located in certain sequence or environments adducted by HNE.

Protein cysteine oxidation in redox signaling: Caveats on sulfenic acid detection and quantification.

Oxidation of critical signaling protein cysteines regulated by HO has been considered to involve sulfenic acid (RSOH) formation. RSOH may subsequently form either a sulfenyl amide (RSNHR') with a neighboring amide, or a mixed disulfide (RSSR') with another protein cysteine or glutathione. Previous studies have claimed that RSOH can be detected as an adduct (e.

Cardiovascular disease and type 2 diabetes in evolutionary perspective: a critical role for helminths?

Heart disease and type 2 diabetes are commonly believed to be rare among contemporary subsistence-level human populations, and by extension prehistoric populations. Although some caveats remain, evidence shows these diseases to be unusual among well-studied hunter-gatherers and other subsistence populations with minimal access to healthcare. Here we expand on a relatively new proposal for why these and other populations may not show major signs of these diseases.

How Does Medicaid Reimbursement Impact Nursing Home Quality? The Effects of Small Anticipatory Changes.

Objective: In 2006, Ohio changed its Medicaid reimbursement methodology for nursing homes (NHs) to promote more efficient staffing levels. This study examines the impacts of this policy change on quality.

Research Design And Subjects: Ohio NHs were categorized based on their anticipated change in reimbursement under a new reimbursement system initiated in 2006.

Cognitive Stimulation for People with Dementia in Long-Term Care Facilities: Baseline Cognitive Level Predicts Cognitive Gains, Moderated by Depression.

Background: Increasing evidence demonstrates the efficacy of cognitive stimulation (CS) in individuals with dementia. However, conducting studies in nursing homes engenders specific challenges that have limited the data gathered on this topic so far.

Objective: The aim of this randomized controlled trial was to investigate the effects of CS on cognition, quality of life (QoL), behavioral symptoms, and activities of daily life in persons with dementia living in nursing homes.

Screening for Cognitive Impairment in Parkinson's Disease: Improving the Diagnostic Utility of the MoCA through Subtest Weighting.

Background: Given the high prevalence of cognitive impairment in Parkinson's disease (PD), cognitive screening is important in clinical practice. The Montreal Cognitive Assessment (MoCA) is a frequently used screening test in PD to detect mild cognitive impairment (PD-MCI) and Parkinson's disease dementia (PD-D). However, the proportion in which the subtests are represented in the MoCA total score does not seem reasonable.

The Proteasome and Oxidative Stress in Alzheimer's Disease.

Significance: Alzheimer's disease is a neurodegenerative disorder that is projected to exceed more than 100 million cases worldwide by 2050. Aging is considered the primary risk factor for some 90% of Alzheimer's cases but a significant 10% of patients suffer from aggressive, early-onset forms of the disease. There is currently no effective Alzheimer's treatment and this, coupled with a growing aging population, highlights the necessity to understand the mechanism(s) of disease initiation and propagation.

Mitochondrial Lon protease in human disease and aging: Including an etiologic classification of Lon-related diseases and disorders.

The Mitochondrial Lon protease, also called LonP1 is a product of the nuclear gene LONP1. Lon is a major regulator of mitochondrial metabolism and response to free radical damage, as well as an essential factor for the maintenance and repair of mitochondrial DNA. Lon is an ATP-stimulated protease that cycles between being bound (at the inner surface of the inner mitochondrial membrane) to the mitochondrial genome, and being released into the mitochondrial matrix where it can degrade matrix proteins.

Verbal memory declines more in female patients with Parkinson's disease: the importance of gender-corrected normative data.

Background: Data on gender-specific profiles of cognitive functions in patients with Parkinson's disease (PD) are rare and inconsistent, and possible disease-confounding factors have been insufficiently considered.

Method: The LANDSCAPE study on cognition in PD enrolled 656 PD patients (267 without cognitive impairment, 66% male; 292 with mild cognitive impairment, 69% male; 97 with PD dementia, 69% male). Raw values and age-, education-, and gender-corrected Z scores of a neuropsychological test battery (CERAD-Plus) were compared between genders.

What is the concentration of hydrogen peroxide in blood and plasma?

The concentration of hydrogen peroxide (H2O2) in blood and plasma is a measurement that has often been made, but the absolute values remain unsettled due the great variability of results actually published in the literature. As in every tissue, the concentration of H2O2 in blood and plasma is determined by the dynamics of its production versus its removal. The major sources of H2O2 in cells will only be briefly described as they are already well documented, The production of H2O2 in red blood cells will be described as it is less well known.

Degradation of oxidized proteins by the proteasome: Distinguishing between the 20S, 26S, and immunoproteasome proteolytic pathways.

The proteasome is a ubiquitous and highly plastic multi-subunit protease with multi-catalytic activity that is conserved in all eukaryotes. The most widely known function of the proteasome is protein degradation through the 26S ubiquitin-proteasome system, responsible for the vast majority of protein degradation during homeostasis. However, the proteasome also plays an important role in adaptive immune responses and adaptation to oxidative stress.

New Directions for Social Services: Much Ado About Nothing.

This article raises the question about whether or not our social services programs are taking new directions or whether there is much ado about nothing. Demographic data and their social implications are presented as background for the discussion. While rhetoric may have changed, the general impression is that we are walking in an Heraclitian stream in which there is both sameness and change.

Adaptive homeostasis.

Homeostasis is a central pillar of modern Physiology. The term homeostasis was invented by Walter Bradford Cannon in an attempt to extend and codify the principle of 'milieu intérieur,' or a constant interior bodily environment, that had previously been postulated by Claude Bernard. Clearly, 'milieu intérieur' and homeostasis have served us well for over a century.

The Immunoproteasome in oxidative stress, aging, and disease.

The Immunoproteasome has traditionally been viewed primarily for its role in peptide production for antigen presentation by the major histocompatibility complex, which is critical for immunity. However, recent research has shown that the Immunoproteasome is also very important for the clearance of oxidatively damaged proteins in homeostasis, and especially during stress and disease. The importance of the Immunoproteasome in protein degradation has become more evident as diseases characterized by protein aggregates have also been linked to deficiencies of the Immunoproteasome.

Glutathione - From antioxidant to post-translational modifier.

Helmut Sies is one of the leading investigators in the multiple roles of glutathione (GSH) in biology. He has pioneered work on the role of GSH in preventing oxidative stress, in transport of GSSG, in protection of protein thiols from irreversible oxidation through mixed disulfide formation and demonstrated a role of protein glutathionylation in response to hormonal stimulation well before redox signaling became a major subject of investigation. Here I will describe the roles of GSH in several aspects of biology, the work of my laboratory in those findings, and how Helmut Sies work influenced our studies.

The Oxygen Paradox, oxidative stress, and ageing.

Professor Helmut Sies is being lauded in this special issue of Archives of Biochemistry & Biophysics, on the occasion of his retirement as Editor-in-Chief. There is no doubt that Helmut has exerted an enormously positive influence on this journal, the fields of Biochemistry & Biophysics in general, and the areas of free radical and redox biology & medicine in particular. Helmut Sies' many discoveries about peroxide metabolism, glutathione, glutathione peroxidases, singlet oxygen, carotenoids in general and lycopene in particular, and flavonoids, fill the pages of his more than 600 publications.

Transit of H2O2 across the endoplasmic reticulum membrane is not sluggish.

Cellular metabolism provides various sources of hydrogen peroxide (H2O2) in different organelles and compartments. The suitability of H2O2 as an intracellular signaling molecule therefore also depends on its ability to pass cellular membranes. The propensity of the membranous boundary of the endoplasmic reticulum (ER) to let pass H2O2 has been discussed controversially.

Measuring positive attitudes toward persons with dementia: A validation of the Allophilia scale.

Efforts to combat ageism typically focus on negative attitudes toward members of an out-group. Changing attitudes also requires assessment and enhancement of positive attitudes. This study examined the psychometric properties of Allophilia scale when used to measure college students' positive attitudes toward persons with dementia.

Residential Reasoning and the Tug of the Fourth Age.

Purpose Of The Study: Where to grow older occupies the minds of many aging adults. This study examines how anticipation of the fourth age influences third-age residential reasoning. It also investigates the role of social relationships in choosing housing for later life.

The peroxisomal Lon protease LonP2 in aging and disease: functions and comparisons with mitochondrial Lon protease LonP1.

Peroxisomes are ubiquitous eukaryotic organelles with the primary role of breaking down very long- and branched-chain fatty acids for subsequent β-oxidation in the mitochondrion. Like mitochondria, peroxisomes are major sites for oxygen utilization and potential contributors to cellular oxidative stress. The accumulation of oxidatively damaged proteins, which often develop into inclusion bodies (of oxidized, aggregated, and cross-linked proteins) within both mitochondria and peroxisomes, results in loss of organelle function that may contribute to the aging process.

Genetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum.

DNA methylation (DNAm) levels lend themselves for defining an epigenetic biomarker of aging known as the 'epigenetic clock'. Our genome-wide association study (GWAS) of cerebellar epigenetic age acceleration identifies five significant (P<5.0 × 10(-8)) SNPs in two loci: 2p22.

Redox homeostasis: The Golden Mean of healthy living.

The notion that electrophiles serve as messengers in cell signaling is now widely accepted. Nonetheless, major issues restrain acceptance of redox homeostasis and redox signaling as components of maintenance of a normal physiological steady state. The first is that redox signaling requires sudden switching on of oxidant production and bypassing of antioxidant mechanisms rather than a continuous process that, like other signaling mechanisms, can be smoothly turned up or down.