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Soluble DPP4 originates in part from bone marrow cells and not from the kidney

Publication date: Available online 26 May 2014 Source:Peptides

Author(s): Zhendi Wang , Christina Grigo , Julia Steinbeck , Stephan von Hörsten , Kerstin Amann , Christoph Daniel

Dipeptidyl peptidase 4 (DPP4) is known to inactivate incretins as well as important chemokines and neuropeptides. DPP4 is expressed as a transmembrane protein but also occurs as a soluble enzyme circulating in the blood. However, the origin of the soluble DPP4 (sDPP4) is still unknown. In this study, DPP4 activity was quantified in plasma and extracted from different rat organs. Then, in order to see if the kidney or the bone marrow was the source of sDPP4, kidney or bone marrow transplantation were performed between wildtype (wt) Dark Agouti (DA) and DPP4 deficient congenic rats (n=6-9). Kidney was verified to have the highest DPP4 activity, followed by spleen and lung. In the following three weeks after successful kidney transplantation only transient trace plasma DPP4 activity was detected in DPP4 deficient rats receiving wt kidneys. In addition, DPP4 activity was not diminished in DA wt rats receiving DPP4 deficient kidneys. Both findings indicated that sDPP4 did not originate from the kidney. In contrast, 43±14% (compared to wt) sDPP4 activity was detected in the plasma of DPP4 deficient DA rats that were reconstituted with wt bone marrow cells. Not only leukocyte but also macrophage subpopulations express DPP4 in bone marrow as well as in blood as assessed by flow cytometry. Thus, bone marrow derived cells but not the kidney represent at least one source of sDPP4. And leukocyte or macrophage subpopulations could be potential candidates.





Effects of PEGylated porcine glucagon-like peptide-2 therapy in weaning piglets challenged with lipopolysaccharide

Publication date: Available online 26 May 2014 Source:Peptides

Author(s): Ke-ke Qi , Jie Wu , Zi-wei Xu

This study aims to evaluate the therapeutic effect of polyethylene glycosylated porcine glucagon-like peptide-2 (pGLP-2), a long-acting form of pGLP-2, in lipopolysaccharide (LPS)-challenged piglets. Eighteen 21-day-old weaning piglets were randomly assigned into three groups: control (saline solution), LPS (100μg/kg LPS), and PEG–pGLP-2 (10 nmol/kg PEG–pGLP-2+100 μg/kg LPS). All treatments were administered intraperitoneally. Compared with the control treatment, LPS treatment significantly decreased (P <0.05) the villus heights of the duodenum and jejunum, as well as the villus height/crypt depth ratio of the jejunum. However, PEG–pGLP-2 therapy reduced these effects (P >0.05). Specifically, PEG–pGLP-2 infusion significantly increased the villus height/crypt depth ratio of the duodenum (P <0.05) compared with LPS treatment. Compared with the control treatment, LPS treatment significantly increased (P <0.05) the mRNA expression levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in the jejunum. However, PEG–pGLP-2 therapy reduced these effects (P <0.05). Specifically, PEG–pGLP-2 infusion significantly decreased (P <0.05) the mRNA expression levels of interleukin (IL)-8 and TNF-α in the duodenum and jejunum, IL-10 in the duodenum, and IFN-γ in the jejunum compared with the LPS treatment. LPS treatment increased the caspase-3 activity of the ileum mucosal (P <0.05), and this effect was significantly reduced by PEG–pGLP-2 treatment. These results indicate that PEG–pGLP-2 infusion alleviates the severity of intestinal injury in weaning piglets by reducing the secretion of inflammatory cytokines and the caspase-3 activity, and increasing the villus height/crypt depth ratio.





Orexin A-induced anxiety-like behavior is mediated through GABA-ergic, α- and β-adrenergic neurotransmissions in mice

Publication date: Available online 26 May 2014 Source:Peptides

Author(s): Miklós Palotai , Gyula Telegdy , Miklós Jászberényi

Orexins are hypothalamic neuropeptides, which are involved in several physiological functions of the central nervous system, including anxiety and stress. Several studies provide biochemical and behavioral evidence about the anxiogenic action of orexin A. However, we have little evidence about the underlying neuromodulation. Therefore, the aim of the present study was to investigate the involvement of neurotransmitters in the orexin A-induced anxiety-like behavior in elevated plus maze (EPM) test in mice. Accordingly, mice were pretreated with a non-selective muscarinic cholinergic antagonist, atropine; a γ-aminobutyric acid subunit A (GABA-A) receptor antagonist, bicuculline; a D2, D3, D4 dopamine receptor antagonist, haloperidol; a non-specific nitric oxide synthase (NOS) inhibitor, nitro-L-arginine; a nonselective α-adrenergic receptor antagonist, phenoxybenzamine and a β-adrenergic receptor antagonist, propranolol 30minutes prior to the intracerebroventricular administration of orexin A. The EPM test started 30min after the i.c.v. injection of the neuropeptide. Our results show that orexin A decreases significantly the time spent in the arms (open/open+closed) and this action is reversed by bicuculline, phenoxybenzamine and propranolol, but not by atropine, haloperidol or nitro-L-arginine. Our results provide evidence for the first time that the orexin A-induced anxiety-like behavior is mediated through GABA-A-ergic, α- and β- adrenergic neurotransmissions, whereas muscarinic cholinergic, dopaminergic and nitrergic neurotransmissions may not be implicated.





Gayle & Richard Olson prize pages

Publication date: June 2014 Source:Peptides, Volume 56







IFC (editorial board)

Publication date: June 2014 Source:Peptides, Volume 56







The International Neuropeptide society pages

Publication date: June 2014 Source:Peptides, Volume 56







Biochemical and physiological characterization of a new Na+-channel specific peptide from the venom of the Argentinean scorpion Tityus trivittatus

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.





How does stress possibly affect cardiac remodeling?

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 (

χ ( 1 ) 2 = 0.178

, 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.





Decreased saliva/serum irisin concentrations in the acute myocardial infarction promising for being a new candidate biomarker for diagnosis of this pathology

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.





Changes in urine levels of substance P, vasoactive intestinal peptide and calcitonin-gene-related peptide in patients with urinary tract infections

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.






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