Peptides最新文献

Vasopressin (VP) is a nonapeptide made of nine amino acids synthesized by the hypothalamus and released by the pituitary gland. VP acts as a neurohormone, neuropeptide and neuromodulator and plays an important role in the regulation of water balance, osmolarity, blood pressure, body temperature, stress response, emotional challenges, etc. Traditionally VP is known to regulate the osmolarity and tonicity. VP and its receptors are widely expressed in the various region of the brain including cortex, hippocampus, basal forebrain, amygdala, etc. VP has been shown to modulate the behavior, stress response, circadian rhythm, cerebral blood flow, learning and memory, etc. The potential role of VP in the regulation of these neurological functions have suggested the therapeutic importance of VP and its analogues in the management of neurological disorders. Further, different VP analogues have been developed across the world with different pharmacotherapeutic potential. In the present work authors highlighted the therapeutic potential of VP and its analogues in the treatment and management of various neurological disorders.

Endogenous opioid peptides serve as potent analgesics through the opioid receptor (OR) activation. However, they often suffer from poor metabolic stability, low lipophilicity, and low blood-brain barrier permeability. Researchers have developed many strategies to overcome the drawbacks of current pain medications and unwanted biological effects produced by the interaction with opioid receptors. Here, we tested multifunctional enkephalin analogs LYS739 (MOR/DOR agonist and KOR partial antagonist) and LYS744 (MOR/DOR agonist and KOR full antagonist) under in vivo conditions in comparison with MOR agonist, morphine. We applied 2D electrophoretic resolution to investigate differences in proteome profiles of crude membrane (CM) fractions isolated from the rat brain cortex and hippocampus exposed to the drugs (10 mg/kg, seven days). Our results have shown that treatment with analog LYS739 induced the most protein changes in cortical and hippocampal samples. The identified proteins were mainly associated with energy metabolism, cell shape and movement, apoptosis, protein folding, regulation of redox homeostasis, and signal transduction. Among these, the isoform of mitochondrial ATP synthase subunit beta (ATP5F1B) was the only protein upregulation in the hippocampus but not in the brain cortex. Contrarily, the administration of analog LYS744 caused a small number of protein alterations in both brain parts. Our results indicate that the KOR full antagonism, together with MOR/DOR agonism of multifunctional opioid ligands, can be beneficial in treating chronic pain states by reducing changes in protein expression levels but retaining analgesic efficacy.

Neuropeptide FF (NPFF) is an octapeptide that regulates various cellular processes, especially pain perception. Recently, there has been a growing interest in understanding the modulation of NPFF in neuroendocrine inflammation. This review aims to provide a thorough overview of the regulation of NPFF in macrophage-mediated biological processes. We delve into the impact of NPFF on macrophage polarization, self-renewal modulation, and the promotion of mitophagy, facilitating the transition from thermogenic fat to fat-storing adipose tissue. Additionally, we explore the NPFF-dependent regulation of the inflammatory response mediated by macrophages, its impact on the differentiation of macrophages, and its capacity to induce alterations in the transcriptome of macrophages. We also address the potential of NPFF as a therapeutic molecule in the field of neuroendocrine inflammation. Overall, our work offers an understanding of the influence of NPFF on macrophage, facilitating the exploration of its pharmacological significance in future studies.

Myoregulin is a recently discovered micropeptide that controls calcium levels by inhibiting the intracellular calcium pump sarco-endoplasmic reticulum Ca²⁺-ATPase (SERCA). Keeping calcium levels balanced in the heart is essential for normal heart functioning, thus myoregulin has the potential to be a crucial regulator of cardiac muscle performance by reducing the rate of intracellular Ca²⁺ uptake. We provide the first report of myoregulin mRNA expression in human heart tissue, absence of expression in human plasma, and the effects of myoregulin on cardiac hemodynamics in an ex vivo Langendorff isolated rat heart model of ischemia/reperfusion. In this preliminary study, myoregulin provided a cardio-protective effect, as assessed by preservation of left ventricular contractility and relaxation, during ischemia/reperfusion. This study provides the foundation for future research in this area.

Abaecin is a natural antimicrobial peptide (AMP) rich in proline from bees. It is an important part of the innate humoral immunity of bees and has broad-spectrum antibacterial ability. This study aimed to determine the effect of Abaecin on dextran sulfate sodium (DSS) -induced ulcerative colitis (UC) in mice and to explore its related mechanisms. Twenty-four mice with similar body weight were randomly divided into 4 groups. 2.5% DSS was added to drinking water to induce colitis in mice. Abaecin and PBS were administered rectally on the third, fifth, and seventh days of the experimental period. The results showed that Abaecin significantly alleviated histological damage and intestinal mucosal barrier damage caused by colitis in mice, reduced the concentration of pro-inflammatory cytokines IL-1β, IL-6, TNF-α, IFN-γ, and the phosphorylation of NF-κB / MAPK inflammatory signaling pathway proteins, and improved the composition of intestinal microorganisms. These findings suggest that Abaecin may have potential prospects for the treatment of UC.

Nisin serves as the prototype within the lantibiotic group of antimicrobial peptides, exhibiting a broad-spectrum inhibition against Gram-positive bacteria, including important food-borne pathogens and clinically relevant antibiotic-resistant strains. The gene-encoded nature of nisin allows for gene-based bioengineering, enabling the generation of novel derivatives. It has been demonstrated that nisin mutants can be produced with improved functional properties. Here, we particularly focus on the uncommon amino acid residues dehydroalanine (Dha) and dehydrobutyrin (Dhb), whose functions are not yet fully elucidated. Prior to this study, we developed a new expression system that utilizes the nisin modification machinery NisBTC to advance expression, resulting in enhanced peptide dehydration efficiency. Through this approach, we discovered that the dehydrated amino acid Dhb at position 18 in the peptide rombocin, a short variant of nisin, displayed four times higher activity compared to the non-dehydrated peptide against the strain Lactococcus lactis. Furthermore, we observed that in the peptides nisin and rombocin, the dehydrated amino acid Dha at residue positon 18 exhibited superior activity compared to the dehydrated amino acid Dhb. Upon purifying the wild-type nisin and its variant nisinG18/Dha to homogeneity, the minimum inhibitory concentration (MIC) indicated that the variant exhibited activity similar to that of wild-type nisin in inhibiting the growth of Bacillus cereus but showed twice the MIC values against the other four tested Gram-positive strains. Further stability tests demonstrated that the dehydrated peptide exhibited properties similar to wild-type nisin under different temperatures but displayed higher resistance to proteolytic enzymes compared to wild-type nisin.

Familial neurohypophyseal diabetes insipidus (FNDI) is a degenerative disorder in which vasopressin-secreting neurons degenerate over time due to the production of mutant proteins. We have demonstrated therapeutic effects of chemical chaperones in an FNDI mouse model, but the complexity and length of this evaluation were problematic. In this study, we established disease-specific mouse induced pluripotent stem cells (iPSCs) from FNDI-model mice and differentiated vasopressin neurons that produced mutant proteins. Fluorescence immunostaining showed that chemical chaperones appeared to protect vasopressin neurons generated from iPSCs derived from FNDI-model mice. Although KCL stimulation released vasopressin hormone from vasopressin neurons generated from FNDI-derived iPSCs, vasopressin hormone levels did not differ significantly between baseline and chaperone-added culture. Semi-quantification of vasopressin carrier protein and mutant protein volumes in vasopressin neurons confirmed that chaperones exerted a therapeutic effect. This research provides fundamental technology for creating in vitro disease models using human iPSCs and can be applied to therapeutic evaluation of various degenerative diseases that produce abnormal proteins.

Type 2 diabetes (T2D) is characterized by peripheral insulin resistance and altered insulin secretion due to a progressive loss of β-cell mass and function. Today, most antidiabetic agents are designed to resolve impaired insulin secretion and/or insulin resistance, and only GLP-1-based formulations contribute to stopping the decline in β-cell mass. HTD4010, a peptide carrying two modifications of the amino acid sequence of INGAP-PP (N-terminus acetylation and substitution of Asn13 by Ala) showed greater plasma stability and could be a good candidate for proposal as a drug that could improve β cell mass and function lost in T2D. In the present study, we showed that HTD4010 included in the culture media of normal rat islets at a dose 100 times lower than that used for INGAP-PP was able to modulate, in the same way as the original peptide, both insulin secretion in response to glucose and the expression of key genes related to insular function, insulin and leptin intracellular pathways, neogenesis, apoptosis, and inflammatory response. Our results confirm the positive effect of HTD4010 on β-cell function and gene expression of factors involved in the maintenance of β-cell mass. Although new assays in animal models of prediabetes and T2D must be performed to be conclusive, our results are very encouraging, and they suggest that the use of HTD4010 at a dose 100 times lower than that of INGAP-PP could minimize its side effects in a future clinical trial.