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Donor organ damage caused by cold preservation is a major problem affecting liver transplantation. Cold preservation most easily damages liver sinusoidal endothelial cells (LSECs), and information about the molecules modulating LSECs function can provide the basis for new therapeutic strategies. Adrenomedullin (AM) is a peptide known to possess anti-apoptotic and anti-inflammatory properties. AM is...
We report the identification of potent agonists of the Glucagon-Like Peptide-1 Receptor (GLP-1R). These compounds are short, 11 amino acid peptides containing several unnatural amino acids, including (in particular) analogs of homohomophenylalanine (hhPhe) at the C-terminal position. Typically the functional activity of the more potent peptides in this class is in the low picomolar range in an in...
Plant-specific insert domain (PSI) is a region of approximately 100 amino acid residues present in most plant aspartic protease (AP) precursors. PSI is not a true saposin domain; it is the exchange of the N- and C-terminal portions of the saposin like domain. Hence, PSI is called a swaposin domain. Here, we report the cloned, heterologous expression and purification of PSI from StAsp 1 (Solanum tuberosum...
The anti-hypertensive peptide Arg-Ile-Tyr, which was isolated based on its inhibitory activity (IC 50 =28μM) for angiotensin I-converting enzyme (ACE) from the subtilisin digest of rapeseed protein, exhibited vasorelaxing activity (EC 50 =5.1μM) in an endothelium-dependent manner in the mesenteric artery of spontaneously hypertensive rats (SHRs). We named the peptide rapakinin. ACE...
N-cadherin is a cell adhesion molecule that promotes axon outgrowth and synapse formation during the development of the central nervous system. In addition, N-cadherin promotes glial cell adhesion and myelination of axons. Therefore, stimulating N-cadherin function with N-cadherin agonists could be used therapeutically to promote regeneration of the nervous system and remyelination after injury or...
A palmitoyl conjugate of an insect pentapeptide that occurs in diapausing insects causes a reversible cell-cycle arrest and suppresses mitochondrial respiration. This peptide compound also causes growth arrest in murine leukemic cell line expressing human gene Bcr/Abl and a farnesoyl peptide induces embryonic diapause in Bombyx mori. These results demonstrate that the insect peptide compounds can...
Targeting splicing machinery components is an underdeveloped strategy for cancer therapy. Uridine-rich small nuclear ribonucleoproteins (UsnRNPs) are essential spliceosome components that recognize splice sites in newly transcribed RNA. The major spliceosomal snRNPs are comprised of UsnRNA bound by a ring of Sm proteins. The survival of motor neuron (SMN) complex provides specificity for binding of...
Skin kininogens from bombinid toads encode an array of bradykinin-related peptides and one such kininogen from Bombina maxima also encodes the potent bradykinin B2-receptor antagonist, kinestatin. In order to determine if the skin secretion of the closely-related toad, Bombina orientalis, contained a bradykinin inhibitory peptide related to kinestatin, we screened reverse phase HPLC fractions of defensive...
The present study was designed to determine the dose-dependent effects of endothelin-3 (ET-3) on the secretion of ghrelin and growth hormone (GH) and characterize the receptors involved in these effects. Eight Holstein steers were randomly assigned to receive intravenous bolus injections of vehicle (0.1% bovine serum albumin in saline), bovine ET-3 (0.1, 0.4, 0.7 and 1.0μg/kg), IRL1620 (selective...
Neuropeptide S (NPS) regulates various biological functions by selectively activating the NPS receptor (NPSR). Previous studies demonstrated that the non-peptide molecule SHA 68 acts as a selective NPSR antagonist. In the present study the pharmacological profile of SHA 68 has been further investigated in vitro and in vivo. In cells expressing the mouse NPSR SHA 68 was inactive per se up to 10μM while...
The renin–angiotensin system (RAS) is an essential regulator of the blood pressure and body fluid balance, but the processing cascade or role of the tissue RAS remains obscure. Proangiotensin-12 (proang-12), a novel angiotensin peptide recently discovered in rat tissues, is assumed to function as a factor of the tissue RAS. To investigate the tissue production of proang-12, we measured the circulating...
The newly identified neuropeptide S (NPS) is mainly expressed in a group of neurons located between the locus coeruleus and Barrington's nucleus in the brainstem. Central administration of NPS increases motor activity and wakefulness, and it decreases anxiety-like behavior and feeding. The NPS receptor (NPSR) is widely distributed in various brain regions including the ventral tegmental area (VTA)...
Antimicrobial peptides (AMPs) are effective against a wide range of microbes, but still no research results have reported their use in duck disease therapy. Riemerella anatipestifer (RA) is a Gram-negative bacterium which infects ducks and causes very significant economic losses. The minimum inhibitory concentrations (MICs) of epinecidin-1 for the tested RA strains ranged 6.25–50μg/ml, those of the...
Gap junction channels facilitate chemical and electrical communication between adjacent cells. Gap junction protein, connexin (Cx), is expressed in the endothelial cells of vessels, glomerulus, and renin-secreting cells of the kidney. The purpose of this study was to investigate the role of Cx in renin release using Cx-overexpressing As 4.1 cells. The adenovirus-induced Cx overexpression was conducted...
This study was designed to measure the levels of chromogranin A (CgA), ghrelin and obestatin in serum and saliva (including CgA expression in healthy tissue) in epileptic patients to determine any significant differences between these patients and healthy controls. Samples were obtained from a total of 91 subjects: 10 newly-diagnosed primary generalized epilepsy (PGE) patients who had started treatment...
Instability and proteolytic degradation limit the delivery options and in vivo efficacy of many therapeutic peptides. We previously generated a thioether stabilized angiotensin-(1–7) analog, cAng-(1–7), which is resistant against proteolytic degradation in the circulation. We here investigated oral and pulmonary delivery of this compound. In a first step we investigated the in vitro stability of the...
Previous studies showed a significantly reduced level of hemorphins in the serum of diabetes patients. In order to elucidate the biochemical mechanisms responsible for this anomaly, the influence of hemoglobin glycation on hemorphin generation was studied. The glycation of hemoglobin occurs in the blood of diabetes patients and this could modify its enzymatic digestion and the resulting proteolytic...
Biological actions attributed to the adrenomedullin (AM) peptides, AM and AM2, include reduction of arterial pressure and peripheral resistance. While AM has been shown to reduce aldosterone secretion from the adrenal, little information is available regarding possible actions of AM2 on aldosterone. Evidence suggests that AM may act as a functional antagonist to angiotensin II (Ang II) but such a...
Training in rats adapts the portal vein to respond vigorously to sympathetic stimuli even when the animal is re-exposed to exercise. Moreover, changes in the exercise-induced effects of angiotensin II, a potent venoconstrictor agonist, in venous beds remain to be investigated. Therefore, the present study aimed to assess the effects of angiotensin II in the portal vein and vena cava from sedentary...
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