A common cause of amyotrophic lateral sclerosis is mutations in superoxide dismutase-1, which provoke the disease by an unknown mechanism. We have previously found that soluble hydrophobic misfolded mutant human superoxide dismutase-1 species are enriched in the vulnerable spinal cords of transgenic model mice. The levels were broadly inversely correlated with life spans, suggesting involvement in the pathogenesis.
Forkhead box O (FOXO; DAF-16 in worms) transcription factors, which are of vital importance in cell-cycle control, stress resistance, tumor suppression, and organismal lifespan, are largely regulated through nucleo-cytoplasmic shuttling. Insulin signaling keeps FOXO/DAF-16 cytoplasmic, and hence transcriptionally inactive. Conversely, as in loss of insulin signaling, reactive oxygen species (ROS) can activate FOXO/DAF-16 through nuclear accumulation. How ROS regulate the nuclear translocation of FOXO/DAF-16 is largely unknown.
In cystic fibrosis reduced CFTR function may alter redox properties of airway epithelial cells. Redox-sensitive GFP (roGFP1) and imaging microscopy were used to measure the redox potentials of the cytosol, endoplasmic reticulum (ER), mitochondria, and cell surface of cystic fibrosis nasal epithelial cells and CFTR-corrected cells. We also measured glutathione and cysteine thiol redox states in cell lysates and apical fluids to provide coverage over a range of redox potentials and environments that might be affected by CFTR.
BACKGROUND AND OBJECTIVE: Chronic inflammatory bowel disease (IBD) demonstrates some similarities to the dysregulated chronic immunoinflammatory lesion of periodontitis. Trinitrobenzene sulphonic acid (TNBS) and dextran sodium sulphate (DSS) administered to rodents have been shown to elicit inflammatory responses that undermine the integrity of the gut epithelium in a similar manner to IBD in humans. The objective of this study was to evaluate the ability of these chemicals to elicit periodontal inflammation as a novel model for alveolar bone loss.
The Journal of Clinical Endocrinology and Metabolism
OBJECTIVE: In preclinical reports, restriction of dietary methionine intake was shown to enhance metabolic flexibility, improve lipid profiles, and reduce fat deposition. The present report is the outcome of a "proof of concept" study to evaluate the efficacy of dietary methionine restriction (MR) in humans with metabolic syndrome.
BACKGROUND: Herein we report the discovery of a cystine-crosslinked peptide from Porifera along with high-quality spatial details accompanied by the description of its unique effect on neuronal calcium influx. METHODS: Asteropsin A (ASPA) was isolated from the marine sponge Asteropus sp., and its structure was independently determined using X-ray crystallography (0.87 angstroms) and solution NMR spectroscopy.
A novel cystine knot peptide, asteropsin E (ASPE), was isolated from an Asteropus sp. marine sponge. The primary, secondary, and tertiary structures of ASPE were determined by high-resolution 2D NMR spectroscopy (900 MHz). With the exception of an N-terminal modification, ASPE shares properties with the previously reported asteropsins A-D, that is, the absence of basic residues, a highly acidic nature, conserved structurally important residues (including two cis-prolines), and a highly conserved tertiary structural framework.