Peptides最新文献

Neuropeptides are small molecules that mediate intercellular signaling and regulate physiological processes. Starfish possess various myoactive neuropeptides, including starfish myorelaxant peptide (SMP) and a calcitonin-type peptide with apical muscle relaxing properties. In this study, we report the purification of a neuropeptide from starfish (Patiria pectinifera) pyloric caeca extract using high-performance liquid chromatography (HPLC) and an in vitro bioassay to screen for fractions and peptides with relaxing effects on P. pectinifera apical muscle preparations. A series of HPLC steps using reversed-phase and cation-exchange columns yielded a purified peptide with muscle-relaxing effects. The purified peptide's structure was determined by LC-MS and Edman degradation, revealing a pentapeptide with an amidated C-terminus (NGFFYamide) and a molecular mass of 646.2930 Da. This is the first report of NGFFYamide purification from P. pectinifera through biochemical methods. The nucleotide sequence encoding the NGFFYamide precursor was determined, showing the presence of a conserved neurophysin domain in the C-terminal region. RT-qPCR results confirmed high expression in radial nerves cord, consistent with previous findings on NG peptides in echinoderms. In vitro pharmacological studies on muscle preparations from P. pectinifera and Asterias amurensis revealed differential relaxing activity of NGFFYamide on apical muscles, while its effects on tube foot preparations were similar in both species. NGFFYamide also induced potent contraction in P. pectinifera cardiac stomach. Comparison of three NG peptides (NGFFYamide, NGFFFamide, and NGIWYamide) on P. pectinifera cardiac stomach revealed varying potency, suggesting class-specific receptor interactions. Tachyphylaxis was observed in P. pectinifera apical muscle but not in A. amurensis, warranting further investigation. Based on these results, it is plausible that NGFFYamide could be involved in regulating locomotion and feeding behavior in P. pectinifera, consistent with findings in Asterias rubens.

Spexin (SPX) is a 14-amino-acid peptide that plays an important role in the regulation of metabolism and energy homeostasis. It is well known that a variety of bioactive molecules released into the circulation by organs and tissues in response to acute and chronic exercise, known as exerkines, mediate the benefits of exercise by improving metabolic health. However, it is unclear whether acute exercise affects SPX levels in the circulation and peripheral tissues. This study aimed to determine whether acute treadmill exercise induces plasma SPX levels, as well as mRNA expression and immunostaining of SPX in skeletal muscle, adipose tissue, and liver. Male Sprague Dawley rats were divided into sedentary and acute exercise groups. Plasma, soleus (SOL), extensor digitorum longus (EDL), adipose tissue, and liver samples were collected at six time points (0, 1, 3, 6, 12, and 24 h) following 60 min of acute treadmill exercise at a speed of 25 m/min and 0 % grade. Acute exercise increased plasma SPX levels and induced mRNA expression of Spx in the SOL, EDL, and liver. Immunohistochemical analysis demonstrated that acute exercise led to a decrease in SPX immunostaining in the liver. Taken together, these findings suggest that SPX increases in response to acute exercise as a potential exerkine candidate, and the liver may be one of the sources of acute exercise-induced plasma SPX levels in rats. However, a comprehensive analysis is needed to fully elucidate the systemic response of SPX to acute exercise, as well as the tissue from which SPX is secreted.

Aims

It has been reported that some peptides released by the gastro-intestinal tract play important roles in the prevention of myocardial ischemia/reperfusion injury (MIRI). Bombesin (BN) is a biologically active peptide released by non-adrenergic non-cholinergic nerves on the gastric antrum mucosa controlled by the vagus nerve. However, there is a lack of reports on the impact of BN on MIRI. This study aimed to explore the influence of BN on MIRI and its underlying mechanism.

Materials and methods

MIRI was induced by either 30 min of global ischemia in Langendorff perfused rat hearts, or by ligation of the descending coronary artery for 30 min in anesthetized Spraque-Dawley rats, and both were followed by 120 min reperfusion. Infarct size and left ventricular function were assessed, and lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) levels were measured spectrophotometrically, while cardiomyocyte apoptosis was detected by TUNEL assay. The content of BN in plasma was measured with enzyme-linked immunosorbent assays (ELISA). The expression of caspase 3, Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) were quantified.

Key findings

BN and vagus nerve stimulation improved cardiac contractile function and reduced myocardial infarct size, attenuated oxidative stress damage and myocardial cell apoptosis, increased the expression of Keap1, Nrf2, and HO-1. and these effects were blocked by using a BN receptor antagonist.

Significance

BN provides protection against MIRI, and its underlying mechanism is through activation of the Keap1/Nrf2/HO-1 pathway. This research provides more reliable evidence for the "gut-heart axis dialogue" and explores potential therapeutic approaches for MIRI.

Tirzepatide (LY3298176), a GLP-1 and GIP receptor agonist, is fatty-acid-modified and 39-amino acid linear peptide, which ameliorates learning and memory impairment in diabetic rats. However, the specific molecular mechanism remains unknown. In the present study, we investigated the role of tirzepatide in the neuroprotective effects in Alzheimer's disease (AD) model mice. Tirzepatide was administrated intraperitoneal (i.p.) APP/PS1 mice for 8 weeks with at 10 nmol/kg once-weekly, it significantly decreased the levels of GLP-1R, and GFAP protein expression and amyloid plaques in the cortex, it also lowered neuronal apoptosis induced by amyloid-β (Aβ), but did not affect the anxiety and cognitive function in APP/PS1 mice. Moreover, tirzepatide reduced the blood glucose levels and increased the mRNA expression of GLP-1R, SACF1, ATF4, Glu2A, and Glu2B in the hypothalamus of APP/PS1 mice. Tirzepatide increased the mRNA expression of glucose transporter 1, hexokinase, glucose-6-phosphate dehydrogenase, and phosphofructokinase in the cortex. Lastly, tirzepatide improved the energetic metabolism by regulated reactive oxygen species production and mitochondrial membrane potential caused by Aβ, thereby decreasing mitochondrial function and ATP levels in astrocytes through GLP-1R. These results provide valuable insights into the mechanism of brain glucose metabolism and mitochondrial function of tirzepatide, presenting potential strategies for AD treatment.

The neurohormones oxytocin (OT) and arginine vasopressin (AVP) are involved in social behaviors and psychiatric conditions. However, more research on nonhuman primates with complex social behaviors is needed. We studied two closely-related primate species with divergent social and mating systems; hamadryas baboons (Papio hamadryas, n=38 individuals) and anubis baboons (Papio anubis, n=46). We measured OT in cerebrospinal fluid (CSF, n=75), plasma (n=81) and urine (n=77), and AVP in CSF (n=45), and we collected over 250 hours of focal behavioral observations. Using Bayesian multivariate models, we found no clear species difference in hormone levels; the strongest support was for hamadryas having higher CSF OT levels than anubis (posterior probability [PP] for females = 0.75, males = 0.84). Looking at nine specific behaviors, OT was associated with affiliative behaviors (approach, proximity, grooming, PP ∼ 0.85 – 1.00), albeit inconsistently across sources of measurement (CSF, plasma, and urine, which were uncorrelated with each other). Most behaviors had low repeatability (R ∼ 0 – 0.2), i.e. they did not exhibit stable between-individual differences (or “personality”), and different behaviors did not neatly coalesce into higher-order factors (or “behavioral syndromes”), which cautions against the use of aggregate behavioral measures and highlights the need to establish stable behavioral profiles when testing associations with baseline hormone levels. In sum, we found some associations between peptides and social behavior, but also many null results, OT levels from different sources were uncorrelated, and our behavioral measures did not indicate clear individual differences in sociability.

bZIP transcription factors can function as homodimers or heterodimers through interactions with their disordered coiled-coil domain. Such dimer assemblies are known to influence DNA-binding specificity and/or the recruitment of binding partners, which can cause a functional switch of a transcription factor from being an activator to a repressor. We recently identified the genomic targets of a bZIP transcription factor called CREB3L1 in rat hypothalamic supraoptic nucleus by ChIP-seq. The objective of this study was to investigate the CREB3L1 protein-to-protein interactome of which little is known. For this approach, we created and screened a rat supraoptic nucleus yeast two-hybrid prey library with the bZIP region of rat CREB3L1 as the bait. Our yeast two-hybrid approach captured five putative CREB3L1 interacting prey proteins in the supraoptic nucleus. One interactor was selected by bioinformatic analyses for more detailed investigation by co-immunoprecipitation, immunofluorescent cellular localisation, and reporter assays in vitro. Here we identify dimerisation hub protein Dynein Light Chain LC8-Type 1 as a CREB3L1 interacting protein that in vitro enhances CREB3L1 activation of target genes.

This paper is the forty-sixth consecutive installment of the annual anthological review of research concerning the endogenous opioid system, summarizing articles published during 2023 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides and receptors as well as effects of opioid/opiate agonists and antagonists. The review is subdivided into the following specific topics: molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors (1), the roles of these opioid peptides and receptors in pain and analgesia in animals (2) and humans (3), opioid-sensitive and opioid-insensitive effects of nonopioid analgesics (4), opioid peptide and receptor involvement in tolerance and dependence (5), stress and social status (6), learning and memory (7), eating and drinking (8), drug and alcohol abuse (9), sexual activity and hormones, pregnancy, development and endocrinology (10), mental illness and mood (11), seizures and neurologic disorders (12), electrical-related activity and neurophysiology (13), general activity and locomotion (14), gastrointestinal, renal and hepatic functions (15), cardiovascular responses (16), respiration and thermoregulation (17), and immunological responses (18).

Signs and symptoms of hypernatremia largely indicate central nervous system dysfunction. Acute hypernatremia can cause demyelinating lesions similar to that observed in osmotic demyelination syndrome (ODS). We have previously demonstrated that microglia accumulate in ODS lesions and minocycline protects against ODS by inhibiting microglial activation. However, the direct effect of rapid rise in the sodium concentrations on microglia is largely unknown. In addition, the effect of chronic hypernatremia on microglia also remains elusive. Here, we investigated the effects of acute (6 or 24 h) and chronic (the extracellular sodium concentration was increased gradually for at least 7 days) high sodium concentrations on microglia using the microglial cell line, BV-2. We found that both acute and chronic high sodium concentrations increase NOS2 expression and nitric oxide (NO) production. We also demonstrated that the expression of nuclear factor of activated T-cells-5 (NFAT5) is increased by high sodium concentrations. Furthermore, NFAT5 knockdown suppressed NOS2 expression and NO production. We also demonstrated that high sodium concentrations decreased intracellular Ca²⁺ concentration and an inhibitor of Na⁺/Ca²⁺ exchanger, NCX, suppressed a decrease in intracellular Ca²⁺ concentrations and NOS2 expression and NO production induced by high sodium concentrations. Furthermore, minocycline inhibited NOS2 expression and NO production induced by high sodium concentrations. These in vitro data suggest that microglial activity in response to high sodium concentrations is regulated by NFAT5 and Ca²⁺ efflux through NCX and is suppressed by minocycline.

Oxytocin (OXT) was discovered in 1906 as a substance that promotes the pregnancy and childbirth. It affects uterine contraction and lactation. Furthermore, as one of its physiological properties, it exerts analgesic effects. The living body has an ascending pathway that transmits pain stimuli from the periphery to the center and a descending pathway that regulates the dorsal horn neurons from the upper center downward. OXT is involved in the pain-inhibitory descending pathway and generally assumed to exert analgesic effects. In this article, we describe the pain-suppressive effects of OXT, among its many physiological effects.