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Publication date: Available online 24 May 2014 Source:Peptides

Author(s): Fredy I.V. Coronas , Elia Diego-García , Rita Restano-Cassulini , Adolfo R. de Roodt , Lourival D. Possani

A new peptide with 61 amino acids cross-linked by 4 disulfide bridges, with molecular weight of 6938.12Da, and an amidated C-terminal amino acid residue was purified and characterized. The primary structure was obtained by direct Edman degradation and sequencing its gene. The peptide is lethal to mammals and was shown to be similar (95% identity) to toxin Ts1 (gamma toxin) from the Brazilian scorpion Tityus serrulatus; it was named Tt1g (from T. trivittatus toxin 1 gamma-like). Tt1g was assayed on several sub-types of Na⁺-channels showing displacement of the currents to more negative voltages, being the hNav1.3 the most affected channel. This toxin displays characteristics typical to the β-type sodium scorpion toxins. Lethality tests and physiological assays indicate that this peptide is probably the most important toxic component of this species of scorpion, known for causing human fatalities in the South American continent.

Publication date: July 2014 Source:Peptides, Volume 57

Author(s): Dejana Popovic , Bosiljka Plecas-Solarovic , Vesna Pesic , Milan Petrovic , Bosiljka Vujisic-Tesic , Bojana Popovic , Svetlana Ignjatovic , Arsen Ristic , Svetozar S. Damjanovic

The aim of this study was to evaluate the predictive value of adrenocorticotropic hormone (ACTH), cortisol and ACTH receptor polymorphism (ACTHRP) for left ventricular (LV) remodeling. Thirty-six elite male athletes, as chronic stress adaptation models, and twenty sedentary age and sex-mached subjects emabarked on standard and tissue Doppler echocardiography to assess cardiac parameters at rest. They performed maximal cardiopulmonary test, which was used as an acute stress model. ACTH and cortisol were measured at rest (10min before test), at beginning, at maximal effort, at 3rd min of recovery, using radioimmunometric and radioimmunoassey techniques, respectively. Promoter region of ACTHR gene (18p11.2) was analysed from blood samples using reverse polymerization reaction with the analysis of restriction fragment length polimorphisam by SacI restriction enzyme. Normal genotype was CTC/CTC, heterozygot for ACTHRP CTC/CCC and homozygot CCC/CCC. In all participants, ACTH and cortisol increased during acute stress, whereas in recovery ACTH increased and cortisol remained unchanged. 49/56 examiners manifested CTC/CTC, 7/56 CTC/CCC and 0/56 CCC/CCC. There was no difference in ACTHRP frequency between groups (

, p =0.67). LV mass (LVM) and LV end-diastolic volume (LVVd) were higher in athletes than in controls (p <0.01) and lower in CTC/CTC than in CTC/CCC genotype (219.43±46.59(SD)g vs. 276.34±48.86(SD)g, p =0.004; 141.24±24.46(SD)ml vs. 175.29±37.07(SD)ml, p =0.002; respectively). In all participants, predictors of LVM and LVVd were ACTH at rest (B =−1.00,−0.44; β =−0.30,−0.31; p =0.026,0.012, respectively) and ACTHRP (B =56.63,34; β =0.37,0.40; p =0.003,0.001, respectively). These results demonstrate that ACTH and ACTHRP strongly predict cardiac morphology suggesting possible regulatory role of stress system activity and sensitivity in cardiac remodeling.

Publication date: June 2014 Source:Peptides, Volume 56

Author(s): Suna Aydin , Suleyman Aydin , Mehmet Ali Kobat , Mehmet Kalayci , Mehmet Nesimi Eren , Musa Yilmaz , Tuncay Kuloglu , Evrim Gul , Ozlem Secen , Omer Dogan Alatas , Adil Baydas

Irisin is a muscle-secreted protein. Cardiac muscle produces more irisin than skeletal muscle in response to acute exercise, and is associated with myocardial infarction (MI) in an experimental model induced by isoproterenol in rats. The timing and significance of its release in patients with acute myocardial infarction (AMI) needs further investigation. We have studied the relationship between serum/saliva irisin concentration and AMI in humans. Serum and saliva samples were taken within 3 days of admission in 11 patients with AMI and in 14 matched controls. Salivary gland irisin was detected immunohistochemically, and serum and saliva levels were measured by ELISA. The three major paired salivary glands (submandibular, sublingual and parotid) produce and release irisin into saliva. Troponin-I, CK, CK-MB concentrations in the AMI group gradually increased from up to 12h, while saliva and serum irisin gradually decreased from up to 48h, compared with the control group (P <0.05). After 12h, troponin-I, CK, CK-MB started to decrease, while saliva and serum irisin started to increase at 72h. Serum irisin levels correlated with age, while troponin I, CK-MB, and CK were correlated and with saliva irisin in AMI patients. Besides cardiac troponin and CK-MB, irisin adds new diagnostic information in AMI patients, and the gradual decrease of saliva/serum irisin over 48h could be a useful biomarker.

Publication date: June 2014 Source:Peptides, Volume 56

Author(s): Seher Çetinkaya Altuntaş , Tümay İpekçi , Gülşen Yakupoğlu , Nuray Erin

Urinary tract infections (UTI) are important health problems and predisposing causes of UTI are not entirely known. Neuro-immune interactions play an important role in human health and disease. Capsaicin-sensitive sensory nerves which in nerve bladder extensively regulate immune system through neuropeptides such as substance P (SP), calcitonin-gene related peptide (CGRP) and vasoactive intestinal peptide (VIP). In addition these neuropeptides also have anti-bacterial effects. To determine how the levels of these peptides changes during UTI, 67 patients (50–90 years-old) diagnosed with UTI in Akdeniz University Faculty of Medicine Hospital were compared with 37 healthy people 50 years or older as the control group. Additionally, 7 patients with UTI symptoms (dysuria, urgency) but with sterile pyuria were also included in the study. Urine samples from 15 patients, whose symptoms regressed with control urine cultures being sterile, were taken after completion of the treatments. Urine neuropeptide levels were determined by ELISA. CGRP levels are significantly higher in patients with UTI, but did not associate with pyuria whereas SP and VIP levels were significantly lower in patients with sterile pyuria, indicating sensory nerve deficiency. Since CGRP exerts immunosuppressive effects, increased levels of the peptide may predispose to UTI. Furthermore, the connection between the observed sensory nerve deficiency and sterile pyuria warrants further studies.

Publication date: June 2014 Source:Peptides, Volume 56

Author(s): J. Michael Conlon , Milena Mechkarska , Gordana Radosavljevic , Samir Attoub , Jay D. King , Miodrag L. Lukic , Stephen McClean

Peptidomic analysis of norepinephrine-stimulated skin secretions of the Orinoco lime tree frog Sphaenorhynchus lacteus (Hylidae, Hylinae) revealed the presence of three structurally related host-defense peptides with limited sequence similarity to frenatin 2 from Litoria infrafrenata (Hylidae, Pelodryadinae) and frenatin 2D from Discoglossus sardus (Alytidae). Frenatin 2.1S (GLVGTLLGHIGKAILG.NH2) and frenatin 2.2S (GLVGTLLGHIGKAILS.NH2) are C-terminally α-amidated but frenatin 2.3S (GLVGTLLGHIGKAILG) is not. Frenatin 2.1S and 2.2S show potent bactericidal activity against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MIC ≤16μM) but are less active against a range of Gram-negative bacteria. Frenatin 2.1S (LC50 =80±6μM) and 2.2S (LC50 =75±5μM) are cytotoxic against non-small cell lung adenocarcinoma A549 cells but are less hemolytic against human erythrocytes (LC50 =167±8μM for frenatin 2.1S and 169±7μM for 2.2S). Weak antimicrobial and cytotoxic potencies of frenatin 2.3S demonstrate the importance of C-terminal α-amidation for activity. Frenatin 2.1S and 2.2S significantly (P <0.05) increased production of proinflammatory cytokines IL-1β and IL-23 by lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages and frenatin 2.1S also enhanced production of TNF-α. Effects on IL-6 production were not significant. Frenatin 2.2S significantly downregulated production of the anti-inflammatory cytokine IL-10 by LPS-stimulated cells. The data support speculation that frenatins act on skin macrophages to produce a cytokine-mediated stimulation of the adaptive immune system in response to invasion by microorganisms. They may represent a template for the design of peptides with therapeutic applications as immunostimulatory agents.

Publication date: June 2014 Source:Peptides, Volume 56

Author(s): Tie-Jiang Chen , Qing-Yang Fu , Wu-Quan Wu

High plasma levels of adrenomedullin have been associated with stroke severity and clinical outcomes. This study aimed to analyze plasma levels of adrenomedullin in traumatic brain injury and their association with prognosis. One hundred and forty-eight acute severe traumatic brain injury and 148 sex- and age-matched healthy controls were recruited in this study. Plasma adrenomedullin concentration was measured by enzyme-linked immunosorbent assay. Unfavorable outcome was defined as Glasgow Outcome Scale score of 1–3. Compared to controls, the patients had significantly higher plasma concentrations of adrenomedullin, which were also highly associated negatively with Glasgow Coma Scale score. Plasma adrenomedullin level was proved to be an independent predictor for 6-month mortality and unfavorable outcome of patients in a multivariate analysis. A receiver operating characteristic curve was configured to show that a baseline plasma adrenomedullin level predicted 6-month mortality and unfavorable outcome of patients with high area under curve. The predictive performance of the plasma adrenomedullin concentration was also similar to that of Glasgow Coma Scale score for the prediction of 6-month mortality and unfavorable outcome of patients. In a combined logistic-regression model, adrenomedullin improved the area under curve of Glasgow Coma Scale score for the prediction of 6-month mortality and unfavorable outcome of patients, but the differences did not appear to be statistically significant. Thus, high plasma levels of adrenomedullin are associated with head trauma severity, and may independently predict long-term clinical outcomes of traumatic brain injury.

Publication date: June 2014 Source:Peptides, Volume 56

Author(s): Suleyman Aydin

Homeostasis of energy is regulated by genetic factors, food intake, and energy expenditure. When energy input is greater than expenditure, the balance is positive, which can lead to weight gain and obesity. When the balance is negative, weight is lost. Regulation of this homeostasis is multi-factorial, involving many orexigenic (appetite-stimulating) and anorexigenic (appetite-suppressing) peptide hormones. Peripheral tissues are now known to be involved in weight regulation and research on its endocrine characteristics proceeds apace. Preptin with 34 amino acids (MW 3948Da), adropin with 43 amino acids and a molecular weight of (4999Da), and irisin with 112 amino acids (12587Da), are three newly discovered peptides critical for regulating energy metabolism. Preptin is synthesized primarily in pancreatic beta cells, and adropin mainly in the liver and brain, and many peripheral tissues. Irisin, however, is synthesized principally in the heart muscle, along with peripheral tissues, including salivary glands, kidney and liver. The prime functions of preptin and adropin include regulating carbohydrate, lipid and protein metabolisms by moderating glucose-mediated insulin release. Irisin is an anti-obesitic and anti-diabetic hormone regulating adipose tissue metabolism and glucose homeostasis by converting white to brown adipose tissue. This review offers a historical account of these discovery and function of these peptides, including their structure, and physiological and biochemical properties. Their roles in energy regulation will be discussed. Their measurement in biological fluids will be considered, which will lead to further discussion of their possible clinical value.

Publication date: June 2014 Source:Peptides, Volume 56

Author(s): Yun Wu , Lei Wang , Maojun Zhou , Xiuhua Jiang , Xiaoyan Zhu , Yu Chen , Shaonan Luo , Yuwen You , Zhenghua Ren , Anlong Xu

The conotoxin cysteine framework XV (-C-C-CC-C-C-C-C-), which was named Lt15a, was firstly identified from the cDNA library of Conus litteratus. After that, 18 new framework XV conotoxin sequences were cloned from nine Conus species. Like other conopeptides, the XV-conotoxins have the conserved signal peptide and propeptide, and there are also some conserved residues in their mature peptide. All the framework XV conotoxins were apparently converged into two branches, because of the indel and point mutations occurred in their mature peptides. By fused with thioredoxin and 6×His tag, six XV-conotoxins were successfully expressed in Escherichia coli and purified. Different framework XV conotoxins have distinct biological activities on mice and frogs, and that may be related to the diversity of the toxin sequences. All the six XV-conotoxins had no obvious effects on the sodium currents of DRG neuron cells of Sprague–Dawley (SD) rats. The identification of this framework of conotoxins enriches our understanding of the structural and functional diversity of conotoxin.