Biological Mechanisms of -Nitrosothiol Formation and Degradation: How Is Specificity of -Nitrosylation Achieved?

The modification of protein cysteine residues underlies some of the diverse biological functions of nitric oxide (NO) in physiology and disease. The formation of stable nitrosothiols occurs under biologically relevant conditions and time scales. However, the factors that determine the selective nature of this modification remain poorly understood, making it difficult to predict thiol targets and thus construct informatics networks.

Physiologic Responses to Dietary Sulfur Amino Acid Restriction in Mice Are Influenced by Atf4 Status and Biological Sex.

Background: Dietary sulfur amino acid restriction (SAAR) improves body composition and metabolic health across several model organisms in part through induction of the integrated stress response (ISR).

Objective: We investigate the hypothesis that activating transcription factor 4 (ATF4) acts as a converging point in the ISR during SAAR.

Methods: Using liver-specific or global gene ablation strategies, in both female and male mice, we address the role of ATF4 during dietary SAAR.

Dietary Methionine Restriction Regulates Liver Protein Synthesis and Gene Expression Independently of Eukaryotic Initiation Factor 2 Phosphorylation in Mice.

The phosphorylation of eukaryotic initiation factor 2 (p-eIF2) during dietary amino acid insufficiency reduces protein synthesis and alters gene expression via the integrated stress response (ISR). We explored whether a Met-restricted (MR) diet activates the ISR to reduce body fat and regulate protein balance. Male and female mice aged 3-6 mo with either whole-body deletion of general control nonderepressible 2 () or liver-specific deletion of protein kinase R-like endoplasmic reticulum kinase () alongside wild-type or floxed control mice were fed an obesogenic diet sufficient in Met (0.

Role of GCN2-Independent Signaling Through a Noncanonical PERK/NRF2 Pathway in the Physiological Responses to Dietary Methionine Restriction.

Restricting availability of essential amino acids (EAAs) limits aminoacylation of tRNAs by their cognate EAAs and activates the nutrient-sensing kinase, general control nonderepressible 2 (GCN2). Activated GCN2 phosphorylates eukaryotic initiation factor 2 (eIF2), altering gene-specific translation and initiating a transcriptional program collectively described as the integrated stress response (ISR). Central GCN2 activation by EAA deprivation is also linked to an acute aversive feeding response.

Disrupted Nitric Oxide Metabolism from Type II Diabetes and Acute Exposure to Particulate Air Pollution.

Type II diabetes is an established cause of vascular impairment. Particulate air pollution is known to exacerbate cardiovascular and respiratory conditions, particularly in susceptible populations. This study set out to determine the impact of exposure to traffic pollution, with and without particle filtration, on vascular endothelial function in Type II diabetes.

A controlled trial of acute effects of human exposure to traffic particles on pulmonary oxidative stress and heart rate variability.

Background: For many individuals, daily commuting activities on roadways account for a substantial proportion of total exposure, as well as peak-level exposures, to traffic-related air pollutants (TRAPS) including ultrafine particles, but the health impacts of these exposures are not well-understood. We sought to determine if exposure to TRAPs particles during commuting causes acute oxidative stress in the respiratory tract or changes in heart rate variability (HRV), a measure of autonomic activity.

Methods: We conducted a randomized, cross-over trial in which twenty-one young adults took two 1.

Alteration of peripheral blood monocyte gene expression in humans following diesel exhaust inhalation.

Context: Epidemiologic associations between acutely increased cardiorespiratory morbidity and mortality and particulate air pollution are well established, but the effects of acute pollution exposure on human gene expression changes are not well understood.

Objective: In order to identify potential mechanisms underlying epidemiologic associations between air pollution and morbidity, we explored changes in gene expression in humans following inhalation of fresh diesel exhaust (DE), a model for particulate air pollution.

Materials And Methods: Fourteen ethnically homogeneous (white males), young, healthy subjects underwent 60-min inhalation exposures on 2 separate days with clean filtered air (CA) or freshly generated and diluted DE at a concentration of 300 μg/m(3) PM(2.