Genomes and Genes
Summary: A cyclized derivative of L-GLUTAMIC ACID. Elevated blood levels may be associated with problems of GLUTAMINE or GLUTATHIONE metabolism.
- Abraham E, Palevitch O, Gothilf Y, Zohar Y. Targeted gonadotropin-releasing hormone-3 neuron ablation in zebrafish: effects on neurogenesis, neuronal migration, and reproduction. Endocrinology. 2010;151:332-40 pubmed publisher..The presence of GnRH3 neurons of olfactory region origin in reproductively mature zebrafish is a prerequisite for normal oocyte development and reproduction. ..
- Giagulli C, Noerder M, Avolio M, Becker P, Fiorentini S, Guzman C, et al. Pidotimod promotes functional maturation of dendritic cells and displays adjuvant properties at the nasal mucosa level. Int Immunopharmacol. 2009;9:1366-73 pubmed publisher..Taken together our data suggest the possibility to use pidotimod as adjuvant molecule to facilitate the activation of the innate immune system as well as to promote an effective mucosal and systemic immune response. ..
- Marco H, Gäde G. Biological activity of the predicted red pigment-concentrating hormone of Daphnia pulex in a crustacean and an insect. Gen Comp Endocrinol. 2010;166:104-10 pubmed publisher..Dappu-RPCH with its three substitutions is not active at all in the shrimp at the tested concentration range of up to 30 pmol. ..
- Kaun K, Chakaborty Chatterjee M, Sokolowski M. Natural variation in plasticity of glucose homeostasis and food intake. J Exp Biol. 2008;211:3160-6 pubmed publisher..Finally, rovers have lower adipokinetic hormone (akh) mRNA levels than sitters. Our data suggest that for mediates larval responses to short-term food deprivation by altering food intake and blood glucose levels. ..
- Schilling S, Appl T, Hoffmann T, Cynis H, Schulz K, Jagla W, et al. Inhibition of glutaminyl cyclase prevents pGlu-Abeta formation after intracortical/hippocampal microinjection in vivo/in situ. J Neurochem. 2008;106:1225-36 pubmed publisher..The approach per se offers a strategy for a rapid evaluation of compounds targeting a reduction of pGlu formation at the N-terminus of amyloid peptides. ..
- Cynis H, Scheel E, Saido T, Schilling S, Demuth H. Amyloidogenic processing of amyloid precursor protein: evidence of a pivotal role of glutaminyl cyclase in generation of pyroglutamate-modified amyloid-beta. Biochemistry. 2008;47:7405-13 pubmed publisher..The study provides new cell-based assays for the profiling of small molecule inhibitors of QC and points to conspicuous differences in processing of APP depending on sequence at the beta-secretase cleavage site. ..
- Hansen K, Stafflinger E, Schneider M, Hauser F, Cazzamali G, Williamson M, et al. Discovery of a novel insect neuropeptide signaling system closely related to the insect adipokinetic hormone and corazonin hormonal systems. J Biol Chem. 2010;285:10736-47 pubmed publisher..In particular, this frequent loss of hormonal systems is unique for arthropods compared with vertebrates. ..
- Orbán E, Mezo G, Schlage P, Csík G, Kulić Z, Ansorge P, et al. In vitro degradation and antitumor activity of oxime bond-linked daunorubicin-GnRH-III bioconjugates and DNA-binding properties of daunorubicin-amino acid metabolites. Amino Acids. 2011;41:469-83 pubmed publisher..Moreover, the antitumor activity is influenced by the structure of the metabolites (daunorubicin-amino acid derivatives) and their DNA-binding properties. ..
- Schilling S, Zeitschel U, Hoffmann T, Heiser U, Francke M, Kehlen A, et al. Glutaminyl cyclase inhibition attenuates pyroglutamate Abeta and Alzheimer's disease-like pathology. Nat Med. 2008;14:1106-11 pubmed publisher..The reduction of brain pE-Abeta by inhibition of glutaminyl cyclase offers a new therapeutic option for the treatment of Alzheimer's disease and provides implications for other amyloidoses, such as familial Danish dementia. ..
- Wicher D, Agricola H, Söhler S, Gundel M, Heinemann S, Wollweber L, et al. Differential receptor activation by cockroach adipokinetic hormones produces differential effects on ion currents, neuronal activity, and locomotion. J Neurophysiol. 2006;95:2314-25 pubmed..Our findings also show that AKHs act through the same basic mechanisms on neuronal and nonneuronal cells, and they support an integration of metabolic and neuronal effects in homoeostatic mechanisms. ..
- Ziegler R, Isoe J, Moore W, Riehle M, Wells M. The putative AKH receptor of the tobacco hornworm, Manduca sexta, and its expression. J Insect Sci. 2011;11:40 pubmed publisher..We also compare the M. sexta adipokinetic hormone receptor with the known adipokinetic hormone receptors of other insects and with gonadotropin releasing hormone-like receptors of invertebrates. ..
- Miajlovic H, Fallon P, Irvine A, Foster T. Effect of filaggrin breakdown products on growth of and protein expression by Staphylococcus aureus. J Allergy Clin Immunol. 2010;126:1184-90.e3 pubmed publisher..Atopic dermatitis is associated with loss-of-function mutations in the filaggrin (FLG) gene, accompanied by reduced levels of filaggrin breakdown products on the skin...
- Cynis H, Schilling S, Bodnar M, Hoffmann T, Heiser U, Saido T, et al. Inhibition of glutaminyl cyclase alters pyroglutamate formation in mammalian cells. Biochim Biophys Acta. 2006;1764:1618-25 pubmed..Thus, QC-inhibition should impact bioactivity, stability or even toxicity of pyroglutamyl peptides preventing glutamine and glutamate cyclization. ..
- Sower S, Balz E, Aquilina Beck A, Kavanaugh S. Seasonal changes of brain GnRH-I, -II, and -III during the final reproductive period in adult male and female sea lamprey. Gen Comp Endocrinol. 2011;170:276-82 pubmed publisher..In summary, these data provide evidence that there are seasonal and differential changes of the three GnRHs during this final reproductive period suggesting specific roles for each of the GnRHs in male and female reproduction...
- Chung Davidson Y, Bryan M, Teeter J, Bedore C, Li W. Neuroendocrine and behavioral responses to weak electric fields in adult sea lampreys (Petromyzon marinus). Horm Behav. 2008;54:34-40 pubmed publisher..They also suggest that electrical stimuli mediate different behaviors in feeding-stage and spawning-stage sea lampreys...
- Otis J, Guidot D. Procysteine stimulates expression of key anabolic factors and reduces plantaris atrophy in alcohol-fed rats. Alcohol Clin Exp Res. 2009;33:1450-9 pubmed publisher..Rather, procysteine minimized the extent of plantaris atrophy by inducing components of several anabolic pathways. Therefore, anti-oxidant treatments such as procysteine supplementation may benefit individuals with alcoholic myopathy. ..
- Fenves A, Kirkpatrick H, Patel V, Sweetman L, Emmett M. Increased anion gap metabolic acidosis as a result of 5-oxoproline (pyroglutamic acid): a role for acetaminophen. Clin J Am Soc Nephrol. 2006;1:441-7 pubmed..This undoubtedly is an underdiagnosed condition because measurements of serum and/or urinary 5-oxoproline levels are not readily available. ..
- Mezo G, Czajlik A, Manea M, Jakab A, Farkas V, Majer Z, et al. Structure, enzymatic stability and antitumor activity of sea lamprey GnRH-III and its dimer derivatives. Peptides. 2007;28:806-20 pubmed..In order to find a correlation between the biological and structural features of these compounds, the conformation of lGnRH-III and its dimer derivatives was determined by ECD, VCD, FT-IR and (1)H NMR. ..
- Pederzolli C, Mescka C, Zandoná B, de Moura Coelho D, Sgaravatti A, Sgarbi M, et al. Acute administration of 5-oxoproline induces oxidative damage to lipids and proteins and impairs antioxidant defenses in cerebral cortex and cerebellum of young rats. Metab Brain Dis. 2010;25:145-54 pubmed publisher
- Schlenzig D, Manhart S, Cinar Y, Kleinschmidt M, Hause G, Willbold D, et al. Pyroglutamate formation influences solubility and amyloidogenicity of amyloid peptides. Biochemistry. 2009;48:7072-8 pubmed publisher..The main driving force for the aggregation is apparently an increase in the hydrophobicity and thus an accelerated seed formation. ..
- Kovacs M, Vincze B, Horvath J, Seprodi J. Structure-activity study on the LH- and FSH-releasing and anticancer effects of gonadotropin-releasing hormone (GnRH)-III analogs. Peptides. 2007;28:821-9 pubmed..The activation of GnRH-receptors on pituitary and breast cancer cells requires a specific structure and/or conformation that makes possible to improve the anticancer selectivity of GnRH analogs. ..
- Kuo M, Lou S, Postlethwait J, Chung B. Chromosomal organization, evolutionary relationship, and expression of zebrafish GnRH family members. J Biomed Sci. 2005;12:629-39 pubmed..We propose a model describing the evolution of gnrh genes involving ancestral duplication of the genes followed by selective loss of one gene in some teleosts. ..
- Mandal A, Balaram P. Mass spectrometric identification of pyroglutamic acid in peptides following selective hydrolysis. Anal Biochem. 2007;370:118-20 pubmed
- Schilling S, Lauber T, Schaupp M, Manhart S, Scheel E, Böhm G, et al. On the seeding and oligomerization of pGlu-amyloid peptides (in vitro). Biochemistry. 2006;45:12393-9 pubmed
- Caballeria J, Pares A, Bru C, Mercader J, Garcia Plaza A, Caballeria L, et al. Metadoxine accelerates fatty liver recovery in alcoholic patients: results of a randomized double-blind, placebo-control trial. Spanish Group for the Study of Alcoholic Fatty Liver. J Hepatol. 1998;28:54-60 pubmed..Thus, metadoxine could be useful in the treatment of the early stages of alcoholic liver disease. ..
- La Mantia I, Grillo C, Mattina T, Zaccone P, Xiang M, Di Mauro M, et al. Prophylaxis with the novel immunomodulator pidotimod reduces the frequency and severity of upper respiratory tract infections in children with Down's syndrome. J Chemother. 1999;11:126-30 pubmed..Pidotimod was well tolerated and no clinical, hematological or biochemical side-effects were noted. ..
- Ziegler R, Cushing A, Walpole P, Jasensky R, Morimoto H. Analogs of Manduca adipokinetic hormone tested in a bioassay and in a receptor-binding assay. Peptides. 1998;19:481-6 pubmed..In the bioassay an inactive concentration of Ala4 M-AKH increased the activity of a half optimal concentration of native M-AKH. ..
- Goldsworthy G, Chandrakant S, Opoku Ware K. Adipokinetic hormone enhances nodule formation and phenoloxidase activation in adult locusts injected with bacterial lipopolysaccharide. J Insect Physiol. 2003;49:795-803 pubmed
- Lee G, Park J. Hemolymph sugar homeostasis and starvation-induced hyperactivity affected by genetic manipulations of the adipokinetic hormone-encoding gene in Drosophila melanogaster. Genetics. 2004;167:311-23 pubmed..From these findings, we propose another role for AKH in the regulation of starvation-induced foraging behavior. ..
- Bryan M, Scott A, Cerny I, Young B, Li W. 15Alpha-hydroxyprogesterone in male sea lampreys, Petromyzon marinus L. Steroids. 2004;69:473-81 pubmed..This is the first time that an RIA has detected such high steroid concentrations in lampreys. This finding is suggestive of a role for 15alpha-P in control of reproduction in the sea lamprey. ..
- Aivazis V, Hatzimichail A, Papachristou A, Valeri R, Iuga Donca G. Clinical evaluation and changes of the respiratory epithelium function after administration of Pidotimod in Greek children with recurrent respiratory tract infections. Minerva Pediatr. 2002;54:315-9 pubmed
- Fernandez García A, Butz P, Trierweiler B, Zöller H, Stärke J, Pfaff E, et al. Pressure/temperature combined treatments of precursors yield hormone-like peptides with pyroglutamate at the N terminus. J Agric Food Chem. 2003;51:8093-7 pubmed..The reported reactions could affect the naturally balanced concentration of short-chain peptides in foods and therefore induce unpredictable biological effects. ..
- Rulifson E, Kim S, Nusse R. Ablation of insulin-producing neurons in flies: growth and diabetic phenotypes. Science. 2002;296:1118-20 pubmed..Interestingly, the phenotype of flies lacking IPCs includes certain features of diabetes mellitus. ..
- Migliorati G, D ADAMIO L, Coppi G, Nicoletti I, Riccardi C. Pidotimod stimulates natural killer cell activity and inhibits thymocyte cell death. Immunopharmacol Immunotoxicol. 1992;14:737-48 pubmed..This inhibition appears to be dose-dependent and is also evident against TPA or Ca(++)ionophore-induced apoptosis. ..
- Silva A, Silva C, Ruschel C, Helegda C, Wyse A, Wannmacher C, et al. L-pyroglutamic acid inhibits energy production and lipid synthesis in cerebral cortex of young rats in vitro. Neurochem Res. 2001;26:1277-83 pubmed..The results strongly indicate that PGA impairs brain energy production. If these effects also occur in humans, it is possible that they may contribute to the neuropathology of patients affected by these diseases. ..
- Russo C, Salis S, Dolcini V, Venezia V, Song X, Teller J, et al. Amino-terminal modification and tyrosine phosphorylation of [corrected] carboxy-terminal fragments of the amyloid precursor protein in Alzheimer's disease and Down's syndrome brain. Neurobiol Dis. 2001;8:173-80 pubmed..This study provides evidence that CTFs constitute in human brain a molecular species directly involved in AD pathogenesis and in the development of the AD-like pathology in DS subjects. ..
- Kim S, Rulifson E. Conserved mechanisms of glucose sensing and regulation by Drosophila corpora cardiaca cells. Nature. 2004;431:316-20 pubmed..Thus, Drosophila CC cells are crucial regulators of glucose homeostasis and they use glucose-sensing and response mechanisms similar to islet cells...
- Van Coillie E, Proost P, Van Aelst I, Struyf S, Polfliet M, De Meester I, et al. Functional comparison of two human monocyte chemotactic protein-2 isoforms, role of the amino-terminal pyroglutamic acid and processing by CD26/dipeptidyl peptidase IV. Biochemistry. 1998;37:12672-80 pubmed..These observations indicate that the NH2-terminal pGlu in MCP-2 is necessary for chemotactic activity but also that it protects the protein against degradation by CD26/DPP IV. ..
- Russo C, Violani E, Salis S, Venezia V, Dolcini V, Damonte G, et al. Pyroglutamate-modified amyloid beta-peptides--AbetaN3(pE)--strongly affect cultured neuron and astrocyte survival. J Neurochem. 2002;82:1480-9 pubmed..These findings suggest that formation of N-terminally modified peptides may enhance beta-amyloid aggregation and toxicity, likely worsening the onset and progression of the disease. ..
- Cummins P, O CONNOR B. Pyroglutamyl peptidase: an overview of the three known enzymatic forms. Biochim Biophys Acta. 1998;1429:1-17 pubmed..Pyroglutamyl peptidase activities isolated and characterized from bacterial sources are also reviewed and compared with their mammalian counterparts. ..
- Shpilenya L, Muzychenko A, Gasbarrini G, Addolorato G. Metadoxine in acute alcohol intoxication: a double-blind, randomized, placebo-controlled study. Alcohol Clin Exp Res. 2002;26:340-6 pubmed..Metadoxine could be helpful in the management of acute ethanol intoxication. ..
- Gourgiotis D, Papadopoulos N, Bossios A, Zamanis P, Saxoni Papageorgiou P. Immune modulator pidotimod decreases the in vitro expression of CD30 in peripheral blood mononuclear cells of atopic asthmatic and normal children. J Asthma. 2004;41:285-7 pubmed..Because CD30 has been associated with Th-2 cells, this observation supports the possibility of pidotimod being able to affect the Th-1/Th-2 balance in atopic asthma. ..
- Addolorato G, Ancona C, Capristo E, Gasbarrini G. Metadoxine in the treatment of acute and chronic alcoholism: a review. Int J Immunopathol Pharmacol. 2003;16:207-14 pubmed..In this review the preclinical and clinical results obtained using metadoxine in acute and chronic alcohol intoxication are reported. ..
- Russo C, Saido T, DeBusk L, Tabaton M, Gambetti P, Teller J. Heterogeneity of water-soluble amyloid beta-peptide in Alzheimer's disease and Down's syndrome brains. FEBS Lett. 1997;409:411-6 pubmed..Both pyroglutamate-modified peptides and the full-length A beta form a stable aggregate that is water soluble. The findings point to a crucial role of the aggregated and modified sA beta in the plaque formation and pathogenesis of AD. ..
- Harigaya Y, Saido T, Eckman C, Prada C, Shoji M, Younkin S. Amyloid beta protein starting pyroglutamate at position 3 is a major component of the amyloid deposits in the Alzheimer's disease brain. Biochem Biophys Res Commun. 2000;276:422-7 pubmed..In vitro comparison of Abeta1-42 and Abeta3(pE)-42 showed that Abeta3(pE)-42 is highly prone to oligomerization. These findings suggest that Abeta3(pE)-42 may be particularly important in AD pathogenesis. ..
- Simon E, Vogel M, Fingerhut R, Ristoff E, Mayatepek E, Spiekerkötter U. Diagnosis of glutathione synthetase deficiency in newborn screening. J Inherit Metab Dis. 2009;32 Suppl 1:S269-72 pubmed publisher..Presently, GSS deficiency is not included in newborn screening programmes in Europe. As outcome depends significantly on early start of treatment, routine inclusion of this disorder in newborn screening panels should be considered. ..
- Chelius D, Jing K, Lueras A, Rehder D, Dillon T, Vizel A, et al. Formation of pyroglutamic acid from N-terminal glutamic acid in immunoglobulin gamma antibodies. Anal Chem. 2006;78:2370-6 pubmed..1 buffer at 45 degrees C. To our knowledge, we showed for the first time that glutamic acid residues located at the N-terminus of proteins undergo pyroglutamic acid formation in vitro. ..
- Carey A, Petersen E, Bruce C, Southgate R, Pilegaard H, Hawley J, et al. Discordant gene expression in skeletal muscle and adipose tissue of patients with type 2 diabetes: effect of interleukin-6 infusion. Diabetologia. 2006;49:1000-7 pubmed
- Pappa E, Zompra A, Diamantopoulou Z, Spyranti Z, Pairas G, Lamari F, et al. Structure-activity studies of lGnRH-III through rational amino acid substitution and NMR conformational studies. Biopolymers. 2012;98:525-34 pubmed publisher..In solution, lGnRH-III adopts an extended backbone conformation in contrast to the well-defined ?-turn conformation of GnRH-I. ..
- Bijukumar D, Choonara Y, Murugan K, Choonara B, Kumar P, du Toit L, et al. Design of an Inflammation-Sensitive Polyelectrolyte-Based Topical Drug Delivery System for Arthritis. AAPS PharmSciTech. 2016;17:1075-85 pubmed publisher..In conclusion, the study presents novel nanoparticles which could effectively encapsulate and deliver hydrophobic drugs to the target site, particularly for arthritis. ..