Role Of Endogenous Peptides Research Articles

The Role of Endogenous Peptides in the Systemic Self-Regulation of Organisms

Regulatory peptides are a wide group of biologically active compounds that affect the current physiological processes in living organisms. Peptides are synthesized in the organism of all biological species, from bacteria to mammals. From a biological point of view, the regulatory peptides have a versatile effect on the organism, they can act as neurotransmitters, neuromodulators, hormones, growth factors, cytokines, etc..The regulatory systems are necessary for all multicellular organisms, to control the function of the cell, to unite it, into one whole organism. In the first half of the 20th century, it was believed that, there were three types of such systems: nervous, immune and endocrine. It was considered that, these systems functioned independently andtheir interaction just was an exceptions. In the 60s of the 20th century, was accumulated enough scientific data, according to which the biologically active peptides were the determining factors of the joint action of the above systems.For today, the physicochemical properties, their specific action, synthetic analogues of physiologically active peptides have been explored.The chemical synthesis of regulatory peptides has been implemented and their therapeutic effects on the human body have been proven.The monograph presents the effect of endogenous peptides on various physiological processes in biological organisms, aslo theirstructural construction and mechanisms of action. In addition, there is discussed, the use and perspectives,of both natural and artificial peptides in medicine.

Peptidomic Analysis of Female Reproductive Tract Secretion to Identify Putative Anti-Infection Peptides in the Female Genital System via Nanotechnologies.

The female genital system infections have high-incidence among various gynecological diseases. The role of endogenous peptides in female reproductive tract secretion has been rarely investigated regarding gynecological infections. To identify gynecological infections associated endogenous peptides, a comparative peptidomic profiling of vaginal secretion from sexually mature and perimenopause women was conducted in this study using nanoflow liquid chromatography-tandem mass spectrometer. A total of 3096 peptide fragments originating from 1364 precursor proteins were identified, 102 of which were discrepantly expressed, which included 60 over-expressed peptides and 42 under-expressed peptides in the sexually mature group compared with the perimenopause group. 6 differentially expressed bioactive peptides were identified to be related to immunodeficiency virus (HIV) infections, human papillomavirus (HPV) infections, bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC). MUC4, MUC5A, MUC5B, MUC6, MUC17 and MUC19 peptides originating from mucin family were identified to enhance vaginal mucous immunity against infections. Moreover, with remarkable development of biomedical nanotechnology, the identified potential anti-infection peptides in our study will be useful in diagnosis and treatment of gynecological infections, especially when combined with nanoparticles. In conclusion, our findings will fill the gap on peptidomics for female genital system infections and pave the way for future studies about reproductive tract diseases management.

Peptidomic Analysis of Fetal Heart Tissue for Identification of Endogenous Peptides Involved in Tetralogy of Fallot

Tetralogy of fallot (TOF) is one of the most prevalent types of congenital heart diseases. As a category of bioactive molecules, peptides have been proved to participate in various biological processes. However, the role of endogenous peptides in the pathogenesis of TOF has not been studied. In this study, we performed a comparative peptidomic profile in the fetal heart of TOF and the control group for the first time by liquid chromatography-tandem mass spectrometry. Our data demonstrated that a total of 201 peptides derived from 176 precursor proteins were differentially expressed in the heart tissues of TOF fetuses compared with normal controls, including 41 upregulated peptides and 160 downregulated peptides. After analyzing the characteristics of these differentially expressed peptides and their precursor proteins, we found that these peptides were potentially involved in different biological processes, especially cardiogenesis and congenital anomaly of the cardiovascular system. Interestingly, we detected several extracellular matrix-derived peptides involved in our differentially expressed peptidomic profile. In summary, our study constructed a comparative peptidomic profile from the heart tissues of TOF fetuses and normal controls, and it identified a series of peptides that could potentially participate in heart development and TOF formation. The emergence of our peptidomics study indicated a new perspective to explore the pathogenesis of abnormal heart morphology, especially TOF.

Role of Endogenous Peptides and Enzymes in the Pathogenesis of Acute Pancreatitis: A Review

Acute pancreatitis is an inflammatory disease with the clinical manifestation of acute abdominal pain. Several factors are involved in the pathogenesis of acute pancreatitis. The exact mechanism(s) by which diverse etiological factors induce an attack are still unclear. However, one of the proposed mechanisms for induction of acute pancreatitis is auto-digestion of pancreatic tissues by unwanted activation of pancreatic digestive enzymes. The main objective of this review is to describe the pathogenesis mechanism of acute pancreatitis that are related to various inflammatory and proinflammatory mediators.Keywords: Acute Pancreatitis, Pancreatic Injury, Cytokines, Chemokines, Inflammation

T cell activation enhancement by endogenous pMHC acts for both weak and strong agonists but varies with differentiation state

T cells are extremely sensitive in their ability to find minute amounts of antigenic peptide in the midst of many endogenous peptides presented on an antigen-presenting cell. The role of endogenous peptides in the recognition of foreign peptide and hence in T cell activation has remained controversial for CD8+ T cell activation. We showed previously that in a CD8+ T cell hybridoma, nonstimulatory endogenous peptides enhance T cell sensitivity to antigen by increasing the coreceptor function of CD8. However, others were not able to detect such enhancement in naive and activated CD8+ T cells. Here, we show that endogenous peptides substantially enhance the ability of T cells to detect antigen, an effect measurable by up-regulation of activation or maturation markers and by increased effector function. This enhancement is most pronounced in thymocytes, moderate in naive T cells, and mild in effector T cells. The importance of endogenous peptides is inversely proportional to the agonist activity of the stimulatory peptide presented. Unlike for CD4+ T cells, the T cell receptor of CD8+ T cells does not distinguish between endogenous peptides for their ability to enhance antigen recognition.

The role of endogenous peptides in the development of long-term posttetanic potentiation

Using the model of long-term posttetanic potentiation (LTP) in slices of the olfactory cortex of rat brain, we have tested a hypothesis according to which activation of nerve cells results in a release of neuromodulatory factors into extracellular space; these factors, diffusing over significant distances, are capable of synchronously modifying the initial reactivity of neuronal populations. Using the technique of bioassay, i.e., transfer of perfusate from the tetanized donor slice to the recipient slice, in combination with pharmacological and neurochemical techniques, we found that in response to excitation, the cells of olfactory cortex slices secrete peptides. This observation confirms the above hypothesis. The spectrum of released peptides changes depending on the degree of cell excitation and, in addition, is frequency-dependent. It has been demonstrated that the key target of these peptides are N-methyl-D-aspartate and glutamate receptors. We propose that two peptide pools are involved in the initial and late phases of LTP. The possible significance of peptide cell regulation in mechanisms of neuronal plasticity is discussed.

Haemorrhage increases the pressor effect of angiotensin-(1-7) but not of angiotensin II at the rat rostral ventrolateral medulla.

To evaluate the effects of angiotensins acting at the rostral ventrolateral medulla (RVLM) on the cardiovascular adjustments following haemorrhage. Changes in mean arterial pressure (MAP) and heart rate (HR) produced by micro-injections of angiotensin II (Ang II) and angiotensin (Ang)-(1-7) and different angiotensin antagonists into the RVLM of anaesthetized rats submitted to haemorrhage, were determined. Experiments were performed in 79 urethane-anaesthetized male Wistar rats. Ang-(1-7) (2.5 and 25 pmol), Ang II (25 pmol), [Sar1,Thr8]-Ang II (non-selective angiotensin antagonist, 0.2 nmol), A-779 (Ang-(1-7) antagonist, 0.1 nmol), losartan (AT1 Ang II receptor antagonist, 0.2 nmol) or vehicle (200 nl) were bilaterally micro-injected into the RVLM under basal conditions or 30 min after blood withdrawal (0.6 ml/100 g bodyweight). In additional groups, [Sar1,Thr8]-Ang II, A-779, losartan or vehicle were micro-injected into the RVLM 10 min before bleeding to uncover a possible role of endogenous peptides during haemorrhage. The pressor effect produced by Ang II micro-injection was not altered by haemorrhage. Conversely, haemorrhage significantly increased the magnitude and duration of the pressor effect of Ang-(1-7) at the RVLM. The fall in MAP induced by haemorrhage was similar after micro-injection of vehicle or A-779. However, micro-injection of [Sar1,Thr8]-Ang II significantly reduced the fall in MAP after haemorrhage. A similar finding was obtained with micro-injection of losartan. In addition, while RVLM micro-injection of [Sar1,Thr8]-Ang II or losartan 30 min after blood withdrawn produced MAP changes that were similar to that observed in control animals, micro-injection of A-779 did not significantly alter baseline MAP. These results suggest that changes in the RVLM reactivity to Ang-(1-7) but not Ang II may contribute to the haemodynamic adjustments triggered by acute reductions in blood volume. The data obtained with [Sar1,Thr8]-Ang II and losartan suggest a primary inhibitory role for endogenous Ang II at the RVLM during haemorrhage.

Distribution and characterization of enterostatin-like immunoreactivity in human cerebrospinal fluid

Enterostatins belong to a family of peptides (e.g., Val-Pro-Asp-Pro-Arg, VPDPR; Ala-Pro-Gly-Pro-Arg, APGPR; and Val-Pro-Gly-Pro-Arg, VPGPR) derived from the tryptic cleavage of amino-terminal pentapeptide from procolipase. Pharmacologic studies have suggested a role for these peptides in appetite regulation and insulin secretion. Studies into the distribution of enterostatins or the role of endogenous peptides have not been possible until now due to the lack of a suitable method for assay. Using two polyclonal antibodies raised against VPDPR and APGPR and different chromatographic methods, we have examined the nature and distribution of enterostatin-like immunoreactivity in human cerebrospinal fluid. The results reported here show for the first time the presence of enterostatin-like immunoreactivity in the human cerebrospinal fluid. Further characterization of cerebrospinal fluid enterostatin-like immunoreactivity revealed that it is not due to APGPR, VPGPR, or VPDPR but to another peptide similar to VPDPR.

The role of endogenous peptides in the direct pathway of alloreactivity to human MHC class II molecules expressed on CHO cells.

The role of endogenous peptides in the direct pathway of alloreactivity to human MHC class II molecules expressed on CHO cells.

Biology of Enterostatin. II. Development of Enzyme-Linked Immunosorbent Assay (ELISA) for Enterostatin (Val-Pro-AsP-Pro-Arg), the Procolipase Activation Peptide

Enterostatins belong to a family of pentapeptides (e.g., Val-Pro-Asp-Pro-Arg in pig, horse, dog, and rat; Ala-Pro-GIy-Pro-Arg in human and chicken; and Val-Pro-Gly-Pro-Arg in rat) derived from the amino-terminus of procolipase after the action of trypsin. Pharmacologic studies with Val-Pro-Asp-Pro-Arg have suggested a role for this peptide in appetite regulation and pancreatic insulin secretion. Studies into the distribution of enterostatins or the role of endogenous peptides have not been possible due to the lack of a suitable method for enterostatin assay. To this end, we raised a highly specific antibody and developed an enzyme-linked immunosorbent assay for Val-Pro-Asp-Pro-Arg. Using the newly developed assay we have shown the presence of Val-Pro-Asp-Pro-Arg-like immunoreactivity (2455±440 pmol/g) in the rat brain.

Role of three quantitatively dominant endogenous peptides from HLA-DRB1 ∗0401 molecules in class II specific alloreactivity

Alloreactivity remains an important barrier to organ transplantation and is caused by T cell recognition of foreign histocompatibility antigens (HAg) in two ways: (1) indirect recognition, in which processed HAg peptides are presented by self MHC like any other foreign antigen, and (2) direct recognition, where the foreign MHC itself is recognized in contravention of the T cell recognition rule of self restriction. Whereas the role of endogenous peptides in direct MHC class I specific recognition is now established, their role in class II specific direct alloreactivity remains controversial, since no defined endogenous peptide has been shown to be required for alloreactivity. That mutations resulting in defective antigen processing impair class II specific allostimulation, however, suggests that the endogenous pathway is important for class II as well as class I alloreactivity. We attempted to establish the importance of endogenous peptides for alloreactivity by identifying common sequences of peptides bound by DR molecules of an HLA-DRB1 ★0401 homozygous B cell line. Peptides corresponding to three of these (calreticulin, HLA class I and an unidentified molecule) were used to restimulate established allospecific HLA-Dw4 reactive T cell clones, as well as to sensitize allogeneic T cells de novo in vitro. Xenogeneic chinese hamster ovary (CHO) cells coexpressing the relevant DR allele together with CD80 were used as antigen presenting cells. The role of CD80 could be determined on these cells because (1) they are xenogeneic and (2) they do not express B7 family members bound by CTLA-4Ig. However, we were unable to obtain evidence for allorecognition of any of these three peptides, although alloreactive T cell clones could be obtained only following stimulation of naive T cells by CHO cells in the presence of synthetic peptide, and not after stimulation by DR/CD80-bearing transfectants alone. Therefore, it seems unlikely that the most common endogenous peptides bound to DR molecules of B cell lines are directly relevant to allorecognition and, consequently, that attempts to influence alloreactivity by peptide blockade are unlikely to succeed.

Role of endogenous peptide in human alloreactive cytotoxic T cell responses.

The T x B hybrid 174 x CEM.T2 (T2) has been shown to be defective in the processing of proteins for presentation by MHC class I molecules. It continues, however, to express significant quantities of HLA-A2.1, suggesting that this class I molecule is expressed either in a largely peptide-free form or in association with a small subset of peptides. In this paper T2 was used in conjunction with limiting dilution analysis to provide a direct estimate of the fraction of alloreactive cytotoxic T lymphocytes (CTLs) that were dependent upon the presence of peptides for their recognition of HLA-A2.1. Alloreactive cytotoxic T cell lines generated by stimulation with HLA-A2.1 expressing peripheral blood lymphocytes recognized T2 poorly. Split-well analysis of 240 clonal limiting dilution cultures demonstrated that this reflected the existence of two subpopulations. An average 85% of HLA-A2.1 specific CTLs recognized HLA-A2.1 on normal cells but not on T2. The remainder recognized HLA-A2.1 on both T2 and normal targets. CTL lines with the latter specificity could be generated by using T2 as a stimulator cell. Using target cells that either expressed a lower density of HLA-A2.1 or that expressed HLA-A2 molecules that had been mutated to affect CD8 binding, no significant differences in avidity between T2-reactive and T2-unreactive CTLs were seen. Thus the failure of the majority of alloreactive CTLs to recognize T2 is not a consequence of the lower level of HLA-A2.1 surface expression on this cell, but is instead due to the absence of appropriate epitopes.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of endogenous peptides in the action of narcotics

Role of endogenous peptides in the action of narcotics