Graphical abstract

No abstract

No abstract

Intercellular signaling events mediated by neuropeptides and peptide hormones represent important targets for both basic science and drug discovery. For many bioactive peptides, the protein receptors that transmit information across the receiving cell membrane are not known, severely limiting these signaling pathways as potential therapeutic targets. Identifying the receptor(s) for a given peptide of interest is complicated by several factors. Most notably, cell–cell signaling peptides are generated through dynamic biosynthetic pathways, can act on many different families of receptor proteins, and can participate in complex ligand–receptor interactions that extend beyond a simple one-to-one archetype. Here, we discuss recent methodological advances to identify signaling partners for bioactive peptides. Recent efforts have centered on methods to identify candidate receptors via transcript expression, methods to match peptide–receptor pairs through high throughput screening, and methods to capture direct ligand–receptor interactions using chemical probes. Future applications of the receptor identification approaches discussed here, as well as technical advancements to address their limitations, promise to lead to a greater understanding of how cells communicate to deliver complex physiologies. Importantly, such advancements will likely provide novel targets for the treatment of human diseases within the central nervous and endocrine systems.

No abstract

We studied the immune responses to heat shock protein (Hsp)-27 and pro-oxidant-antioxidant balance (PAB) values in patients with valvular heart disease, but free of angiographically evident coronary artery disease (CAD). Patients who were candidates for valvuloplasty surgery and 30 healthy matched controls were recruited. The anti-Hsp-27 antibody titers were 0.35 ± 0.04 absorbency units (AU) in the valvuloplasty group, being significantly higher than for the controls (0.11 ± 0.02 AU; P < .05). The PAB values were significantly higher in cases (134.67 ± 13.69 Hamidi-Koliakos(HK) unit) when compared with controls (49.78 ± 6.75 HK unit; P < .05). In cases, the ejection fraction was inversely correlated with anti-Hsp-27 antibody (P < .05) but was not significantly related to PAB values (P > .05). Based on the echocardiographic findings, the patients had no evident heart failure, but the high levels of anti-Hsp-27 and PAB values in patients with valvular heart disease may indicate that these variables can be used as markers of heart failure. However, a longitudinal study is required to confirm this hypothesis.

Cell−cell signaling peptides (e.g., peptide hormones, neuropeptides) are among the largest class of cellular transmitters and regulate a variety of physiological processes. To identify and quantify the relative abundances of cell−cell signaling peptides in different physiological states, liquid chromatography−mass spectrometry-based peptidomics workflows are commonly utilized on freshly dissected tissues. In such animal experiments, the administration of general anesthetics is an important step for many research projects. However, acute anesthetic administration may rapidly change the measured abundance of transmitter molecules and metabolites, especially in the brain and endocrine system, which would confound experimental results. The aim of this study was to evaluate the effect of short-term (<5 min) anesthetic administration on the measured abundance of cell−cell signaling peptides, as evaluated by a typical peptidomics workflow. To accomplish this goal, we compared endogenous peptide abundances in the rat pituitary following administration of 5% isoflurane, 200 mg/kg sodium pentobarbital, or no anesthetic administration. Label-free peptidomics analysis demonstrated that acute use of isoflurane changed the levels of a small number of peptides, primarily degradation products of the hormone somatotropin, but did not influence the levels of most other peptide hormones. Acute use of sodium pentobarbital had negligible impact on the relative abundance of all measured peptides. Overall, our results suggest that anesthetics used in pituitary peptidomics studies do not dramatically confound observed results.

This study showed that among Iranian subjects, the inflammatory marker, hs-CRP, was strongly and positively associated with a marker of oxidative stress and also with several traditional risk factors of CVD. Moreover, the impact of traditional cardiovascular risk factors on hs-CRP concentrations and PAB values differed.