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Amino Acids: The Forum for Amino Acid, Peptide and Protein Research (v.32, #3)

Excitatory amino acids in epilepsy: from the clinics to the laboratory by A. Novelli; R. A. R. Tasker (pp. 295-297).

Preconditioning and neurotrophins: a model for brain adaptation to seizures, ischemia and other stressful stimuli by A. M. Marini; X. Jiang; X. Wu; H. Pan; Z. Guo; M. P. Mattson; N. Blondeau; A. Novelli; R. H. Lipsky (pp. 299-304).

The amino acid glutamate, the major excitatory neurotransmitter in the central nervous system, activates receptors coupled to calcium influx. Excessive activation of glutamate receptors in conditions such as severe epileptic seizures or stroke can kill neurons in a process called excitotoxicity. However, subtoxic levels of activation of the N-methyl-D-aspartate (NMDA) type of glutamate receptor elicit adaptive responses in neurons that enhance their ability to withstand more severe stress. A variety of stimuli induce adaptive responses to protect neurons. For example, sublethal ischemic episodes or a mild epileptic insult can protect neurons in a process referred to as tolerance. The molecular mechanisms that protect neurons by these different stressful stimuli are largely unknown but they share common features such as the transcription factor, nuclear factor kappa B (NF-κB), which is activated by ischemic and epileptic preconditioning as well as exposure to subtoxic NMDA concentrations. In this article, we describe stress-induced neuroprotective mechanisms highlighting the role of brain-derived neurotrophic factor (BDNF), a protein that plays a crucial role in neuronal survival and maintenance, neurogenesis and learning and memory.

Keywords: Keywords: Preconditioning – Epilepsy – Neuroprotection – Hippocampus – BDNF – NF-κB

Mechanisms regulating GABAergic inhibitory transmission in the basolateral amygdala: implications for epilepsy and anxiety disorders by V. Aroniadou-Anderjaska; F. Qashu; M. F. M. Braga (pp. 305-315).

The amygdala, a temporal lobe structure that is part of the limbic system, has long been recognized for its central role in emotions and emotional behavior. Pathophysiological alterations in neuronal excitability in the amygdala are characteristic features of certain psychiatric illnesses, such as anxiety disorders and depressive disorders. Furthermore, neuronal excitability in the amygdala, and, in particular, excitability of the basolateral nucleus of the amygdala (BLA) plays a pivotal role in the pathogenesis and symptomatology of temporal lobe epilepsy. Here, we describe two recently discovered mechanisms regulating neuronal excitability in the BLA, by modulating GABAergic inhibitory transmission. One of these mechanisms involves the regulation of GABA release via kainate receptors containing the GluR5 subunit (GluR5KRs). In the rat BLA, GluR5KRs are present on both somatodendritic regions and presynaptic terminals of GABAergic interneurons, and regulate GABA release in an agonist concentration-dependent, bidirectional manner. The relevance of the GluR5KR function to epilepsy is suggested by the findings that GluR5KR agonists can induce epileptic activity, whereas GluR5KR antagonists can prevent it. Further support for an important role of GluR5KRs in epilepsy comes from the findings that antagonism of GluR5KRs is a primary mechanism underlying the antiepileptic properties of the anticonvulsant topiramate. Another mechanism regulating neuronal excitability in the BLA by modulating GABAergic synaptic transmission is the facilitation of GABA release via presynaptic α_1A adrenergic receptors. This mechanism may significantly underlie the antiepileptic properties of norepinephrine. Notably, the α_1A adrenoceptor-mediated facilitation of GABA release is severely impaired by stress. This stress-induced impairment in the noradrenergic facilitation of GABA release in the BLA may underlie the hyperexcitability of the amygdala in certain stress-related affective disorders, and may explain the stress-induced exacerbation of seizure activity in epileptic patients.

Keywords: Keywords: Amygdala – GABA release – Kainate receptors – α₁ adrenoceptors – Epilepsy – Anxiety disorders

Gender-based changes in cognition and emotionality in a new rat model of epilepsy by T. A. Doucette; C. L. Ryan; R. A. Tasker (pp. 317-322).

Epilepsy research relies heavily on animal models that mimic some, or all, of the clinical symptoms observed. We have previously described a new developmental rat model of epilepsy that demonstrates both behavioural seizures and changes in hippocampal morphology. In the current study we investigated whether these rats also show changes in cognitive performance as measured using the Morris water maze task, and emotionality as measured using the Elevated plus maze task. In the water maze, significant differences between male and female rats were found in several performance variables regardless of treatment. In addition, female but not male rats, treated neonatally with domoic acid had significant impairments in learning new platform locations in the water maze. In the elevated plus maze, a significant proportion of female rats spent more time in the open arm of the maze following prior exposure to the maze whereas this effect was not seen in male rats. We conclude that perinatal treatment with low doses of domoic acid results in significant gender-based changes in cognition and emotionality in adult rats.

Keywords: Keywords: Domoic acid – Kainate – Brain development – Morris water maze – Elevated plus maze – Epilepsy

Nefopam is more potent than carbamazepine for neuroprotection against veratridine in vitro and has anticonvulsant properties against both electrical and chemical stimulation by A. Novelli; A. Groppetti; G. Rossoni; B. Manfredi; A. Ferrero-Gutiérrez; A. Pérez-Gómez; C. M. Desogus; M. T. Fernández-Sánchez (pp. 323-332).

Nefopam (NEF) is a known analgesic that has recently been shown to be effective in controlling both neuropathic pain and convulsions in rodents. In this study we compared nefopam to carbamazepine (CBZ), a reference antiepileptic drug (AED), for their ability to protect cerebellar neuronal cultures from neurodegeneration induced by veratridine (VTD). Furthermore, we tested nefopam for protection against both, maximal electroshock-induced seizures (MES), and isoniazid-induced seizures in mice. Both NEF and CBZ were effective in preventing both signs of excitotoxicity and neurodegeneration following exposure of cultures to 5 µM veratridine for 30 min and 24 h, respectively. Concentrations providing full neuroprotection were 500 µM CBZ and 50 µM NEF, while the concentration providing 50% neuroprotection was 200 µM for CBZ and 20 µM for NEF. Neither NEF nor CBZ reduced excitotoxicity following direct exposure of cultures to glutamate, but CBZ failed to reduce increases in intracellular calcium following stimulation of L-type voltage sensitive calcium channels. In vivo, NEF (20 mg/kg i.p.) significantly reduced MES and fully prevented MES-induced terminal clonus (TC). In comparison, NEF was significantly more effective than CBZ in preventing MES, although both drugs were equally effective against MES-induced TC. Furthermore, nefopam provided protection against isoniazid-induced seizures at doses similar to those protecting against MES.

Keywords: Keywords: Nefopam – Carbamazepine – Cultured cerebellar neurons – Seizures – Behaviour

γ-Glutamyl compounds and their enzymatic production using bacterial γ-glutamyltranspeptidase by H. Suzuki; C. Yamada; K. Kato (pp. 333-340).

Some amino acids and peptides, which have low solubility in water, become much more soluble following γ-glutamylation. Compounds become more stable in the blood stream with γ-glutamylation. Several γ-glutamyl compounds are known to have favorable physiological effects on mammals. γ-Glutamylation can improve taste and can stabilize glutamine in aqueous solution. Because of such favorable features, γ-glutamyl compounds are very attractive. However, only a small number of γ-glutamyl amino acids have been studied although many other γ-glutamyl compounds may have characteristics that will benefit humans. This is mainly because γ-glutamyl compounds have not been readily available. An efficient and simple method of producing various γ-glutamyl compounds, especially γ-glutamyl amino acids, using bacterial γ-glutamyltranspeptidase has been developed. With this method, modifications of reactive groups of the substrate and energy source such as ATP are not required, and a wide-range of γ-glutamyl compounds can be synthesized. Moreover, bacterial γ-glutamyltranspeptidase, a catalyst for this method, is readily available from the strain over-producing this enzyme. The superiority of producing γ-glutamyl compounds with bacterial γ-glutamyltranspeptidase over other methods of production is discussed.

Keywords: Keywords: Amino acid – γ-Glutamyl transferase – γ-Glutamyl compounds – γ-Glutamylation – Transpeptidation – Enzymatic production

Nuclear/cytoplasmic localization of Akt activity in the cell cycle by M. Rosner; M. Hanneder; A. Freilinger; M. Hengstschläger (pp. 341-345).

The serine/threonine protein kinase Akt (also known as PKB) is a proto-oncogene and one of the most frequently hyperactivated kinases in human cancer. Its activation downstream of growth-factor-stimulated phosphatidylinositide-3′-OH kinase activity plays a role in the control of cell cycle, cell growth, apoptosis and cell energy metabolism. Akt phosphorylates some thousand downstream substrates, including typical cytoplasmic as well as nuclear proteins. Accordingly, it is not surprising that Akt activity can be found in both, the cytoplasm and the nucleus. Here we report the cell cycle regulation of nuclear and cytoplasmic Akt activity in mammalian cells. These data provide new insights into the regulation of Akt activity and have implications for future studies on the regulation of the wide variety of different nuclear and cytoplasmic Akt substrates.

Keywords: Keywords: Akt – Cell cycle – Nucleus – Cytoplasm

Mass spectrometric analysis of protein histidine phosphorylation by X.-L. Zu; P. G. Besant; A. Imhof; P. V. Attwood (pp. 347-357).

Protein histidine phosphorylation is now recognized as an important form of post-translational modification. The acid-lability of phosphohistidine has meant that this phosphorylation has not been as well studied as serine/threonine or tyrosine phosphorylation. We show that phosphohistidine and phosphohistidine-containing phosphopeptides derived from proteolytic digestion of phosphohistone H4 are detectable by ESI-MS. We also demonstrate reverse-phase HPLC separation of these phosphopeptides and their detection by MALDI-TOF-MS.

Keywords: Keywords: Phosphohistidine – Mass spectrometry – Phosphoamino acid analysis – Histone H4 – Phosphopeptide – Histidine kinase

Cell cycle checkpoints: the role and evaluation for early diagnosis of senescence, cardiovascular, cancer, and neurodegenerative diseases by O. Golubnitschaja (pp. 359-371).

Maintenance of genomic integrity is critical for prevention of a wide variety of adverse cellular effects including apoptosis, cellular senescence, and malignant cell transformation. Under stress conditions and even during an unperturbed cell cycle, checkpoint proteins play the key role in genome maintenance by and mediating cellular response to DNA damage, and represent an essential part of the “cellular stress response proteome”. Intact checkpoint signal transduction cascades check the presence of genome damage, trigger cell cycle arrest, and forward the information to the protein core of cell cycle machinery, replication apparatus, repair, and/or apoptotic protein cores. Genetic checkpoint defects lead to syndromes that demonstrate chromosomal instability, increased sensitivity to genotoxic stress, tissue degeneration, developmental retardation, premature aging, and cancer predisposition that is most extensively studied for the ATM-checkpoint mutated in Ataxia telangiectasia. Tissue specific epigenetic control over the function of cell cycle checkpoints can be, further, misregulated by aberrant DNA methylation status. The consequent checkpoint dysregulation may result in tissue specific degenerative processes such as degeneration and calcification of heart aortic valves, diabetic cardiomyopathy, hyperhomocysteinemic cerebrovascular, peripheral vascular and coronary heart diseases, neurodegenerative disorders (Alzheimer and Parkinson diseases, amyotrophic lateral sclerosis, glaucoma), and accelerated aging frequently accompanied with cancer. This review focuses on the checkpoints shown to be crucial for unperturbed cell cycle regulation, dysregulation of which might be considered as a potential molecular marker for early diagnosis of and therapy efficiency in neurodegenerative, cardiovascular and cancer diseases. An application of the most potent detection technologies such as “Disease Proteomics and Transcriptomics” also considered here, allows a most specific selection of diagnostic markers.

Keywords: Keywords: Stress response proteome – Cell cycle checkpoints – Epigenetic control – Cardiovascular and cancer diseases – Senescence and neurodegeneration – Early diagnosis and follow-up – Disease proteomics and transcriptomics

Non-sufficient cell cycle control as possible clue for the resistance of human malignant glioma cells to clinically relevant treatment conditions by D. Trog; H. Moenkemann; W. Breipohl; H. Schueller; H. Schild; O. Golubnitschaja (pp. 373-379).

Objectives. Human gliomas have a catastrophic prognosis with a median survival in the range of one year even after therapeutic treatment. Relatively high resistance towards apoptotic stimuli is the characteristic feature of malignant gliomas. Since cell cycle control has been shown to be the key mechanism controlling both apoptosis and proliferation, this study focuses on DNA damage analysis and protein expression patterns of essential cell cycle regulators P53 and P21^waf1/cip1 in glioma under clinically relevant therapeutic conditions. Material and methods. U87MG cell line, characterised by wild p53-phenotype relevant for the majority of primary malignant glioblastomas, was used. Glioma cells underwent either irradiation or temozolomide treatment alone, or combined radio/chemo treatment. DNA damage was analysed by the “Comet Assay”. Expression rates of target proteins were analysed using “Western-Blot” technique. Results and conclusions. “Comet Assay” demonstrated extensive DNA damage caused by temozolomide treatment alone and in combination with irradiation, correlating well with the low survival rate observed under these treatment conditions. In contrast, irradiation alone resulted in a relatively low DNA damage, correlating well with a high survival rate and indicating a poor therapeutic efficiency of irradiation alone. Unusually low up-regulation of P53 and P21^waf1/cip1 expression patterns was produced by the hereby tested stressful conditions. A deficit in cell cycle control might be the clue to the high resistance of malignant glioma cells to established therapeutic approaches.

Keywords: Keywords: Glioma therapy – Stress – DNA damage – Comet assay – Cell cycle control – Differential gene expression

Effects of β-alanine supplementation on the onset of neuromuscular fatigue and ventilatory threshold in women by J. R. Stout; J. T. Cramer; R. F. Zoeller; D. Torok; P. Costa; J. R. Hoffman; R. C. Harris; J. O’Kroy (pp. 381-386).

This study examined the effects of 28 days of β-alanine supplementation on the physical working capacity at fatigue threshold (PWC_FT), ventilatory threshold (VT), maximal oxygen consumption ( $dot{ m V}$ O_2-MAX), and time-to-exhaustion (TTE) in women. Twenty-two women (age ± SD 27.4 ± 6.1 yrs) participated and were randomly assigned to either the β-alanine (CarnoSyn™) or Placebo (PL) group. Before (pre) and after (post) the supplementation period, participants performed a continuous, incremental cycle ergometry test to exhaustion to determine the PWC_FT, VT, $dot{ m V}$ O_2-MAX, and TTE. There was a 13.9, 12.6 and 2.5% increase (p < 0.05) in VT, PWC_FT, and TTE, respectively, for the β-alanine group, with no changes in the PL (p > 0.05). There were no changes for $dot{ m V}$ O_2-MAX (p > 0.05) in either group. Results of this study indicate that β-alanine supplementation delays the onset of neuromuscular fatigue (PWC_FT) and the ventilatory threshold (VT) at submaximal workloads, and increase in TTE during maximal cycle ergometry performance. However, β-alanine supplementation did not affect maximal aerobic power ( $dot{ m V}$ O_2-MAX). In conclusion, β-alanine supplementation appears to improve submaximal cycle ergometry performance and TTE in young women, perhaps as a result of an increased buffering capacity due to elevated muscle carnosine concentrations.

Keywords: Keywords: Carnosine – β-Alanine – Ergogenic aids – Electromyography – Cycle ergometry

Synthesis of bis-armed amino acid derivatives via the alkylation of ethyl isocyanoacetate and the Suzuki–Miyaura cross-coupling reaction by S. Kotha; V. R. Shah; S. Halder; R. Vinodkumar; K. Lahiri (pp. 387-394).

Two synthetic routes to bis-armed-α-amino acid derivatives are described. The first route involves alkylation of dibromo derivatives with ethyl isocyanoacetate under phase-transfer catalysis (PTC) conditions. The second route uses a palladium-mediated Suzuki–Miyaura cross-coupling reaction between a DL-4-boronophenylalanine derivative and aromatic diiodo (or dibromo) compounds.

Keywords: Keywords: Alkylation – Amino acids – DL-4-boronophenylalanine – Ethyl isocyanoacetate – Suzuki–Miyaura cross-coupling reaction

Somatostatin analogues, a series of tissue transglutaminase inducers, as a new tool for therapy of mesenchimal tumors of the gastrointestinal tract by G. Palmieri; L. Montella; C. Aiello; F. Barbieri; D. Di Vizio; S. Schulz; S. Beninati; A. Budillon; M. Caraglia; L. Insabato; T. Florio (pp. 395-400).

Imatinib, a tyrosine kinase inhibitor directed against the enzymatic domain of KIT protein, was found to produce dramatic clinical responses in metastatic gastrointestinal stromal tumors (GISTs). However, resistance usually develops thus determining treatment failure. The present study was performed to analyse the expression of somatostatin receptor (SSTR) subtypes, modulators of tissue transglutaminase, in a series of GISTs and leiomyosarcomas by immunohistochemistry to identify a new potential therapeutic target. Sixteen cases (8 males and 8 females, age range: 38–73; 11 GISTs, 4 leiomyosarcomas, 1 leiomyoma) were studied. Immunohistochemical detection of the relevant SSTRs was performed on paraffin-embedded tissue sections, stained with polyclonal antibodies directed against the five somatostatin receptor subtypes. We found 7 out of 16 (44%) tumors expressing all SSTRs and 14 out of 16 (87%) tumors positive for at least 3 subtypes. SSTR2_A was the most represented subtype in the tumors studied, being expressed in approximately 70% of cases exhibiting an intense labeling in most of these cases. The significant expression of SSTRs shown in this series of GISTs and gastrointestinal leiomyosarcomas suggests a potential therapeutic target to be explored alone and/or in combination with other therapeutic agents in the setting of refractory GI stromal tumors.

Keywords: Keywords: GIST – Gastrointestinal leiomyosarcomas – Tissue transglutaminase – Somatostatin receptor – Immunohistochemistry – Imatinib

Enantiopure β³-amino acids-2,2-d₂ via homologation of proteinogenic α-amino acids by R. Caputo; L. Longobardo (pp. 401-404).

A procedure for the synthesis of enantiopure β³-amino acids from proteinogenic α-amino acids, developed by our group a few years ago, has been modified to enable the production of C-2 fully deuterated, C-protected β³-amino acids and, even more important, the synthesis of valuable deuterium labelled N(Boc)-protected chiral synthons, such as 2-aminoalcohols, 2-aminoiodides, and β³-amino nitriles.

Keywords: Keywords: β³-amino acids – α-amino acid homologation – C-2-dideuterated amino acids – 2-aminoalcohols-d₂ – 2-aminoiodides-d₂ – β³-amino nitriles-d₂

The effect of taurine on renal ischemia/reperfusion injury by G. Guz; E. Oz; N. Lortlar; N. N. Ulusu; N. Nurlu; B. Demirogullari; S. Omeroglu; S. Sert; C. Karasu (pp. 405-411).

Ischemia-reperfusion (I/R) injury is one of the most common causes of renal dysfunction. Taurine is an endogenous antioxidant and a membrane-stabilizing, intracellular, free beta-amino acid. It has been demonstrated to have protective effects against I/R injuries to tissues other than kidney. The aim of this study was to determine whether taurine has a beneficial role in renal I/R injury. Forty Wistar-Albino rats were allocated into four groups as follows: sham, taurine, I/R, and I/R + taurine. Taurine 7.5 mg/kg was given intra-peritoneally to rats in the groups taurine and I/R + taurine. Renal I/R was achieved by occluding the renal arteries bilaterally for 40 min, followed by 6 h of reperfusion. Immediately thereafter, blood was drawn and tissue samples were harvested to measure 1) serum levels of BUN and creatinine; 2) serum and/or tissue levels of malondialdehyde (MDA), glutathione (GSH), glucose 6-phosphate dehydrogenase (G-6PD), 6-phosphogluconate dehydrogenase (6-PGD) and glutathione reductase (GSH-red); 3) renal morphology; and 4) immunohistochemical staining for P-selectin. Taurine administration reduced I/R-induced increases in serum BUN and creatinine, and serum and tissue MDA levels (p < 0.05). Additionally, taurine lessened the reductions in serum and tissue glutathione levels secondary to I/R (p < 0.05). Taurine also attenuated histopathologic evidence of renal injury, and reduced I/R-induced P-selectin immunoreactivity (p < 0.05). Overall, then, taurine administration appears to reduce the injurious effects of I/R on kidney.

Keywords: Keywords: Taurine – Ischemia – Reperfusion – Kidney – Malondialdehyde and glutathione

Protective effect of taurine on respiratory burst activity of polymorphonuclear leukocytes in endotoxemia by M. Ekremoğlu; N. Türközkan; H. Erdamar; Y. Kurt; H. Yaman (pp. 413-417).

The aim of this study was to evaluate the effect of endotoxin on PMN leukocyte respiratory burst activity by measuring G6PD, NADPH oxidase and XO activities in guinea pig. In addition, the possible protective role of taurine against endotoxin-mediated PMN leukocyte function was examined. All experiments were performed with four groups (control, taurine, endotoxemia, taurine plus endotoxin) of ten guinea pigs. After the endotoxin was administrated (4 mg/kg) both G6PD and NADPH oxidase activities were significantly reduced compared with the control group. NADPH oxidase activity returned to the control value and G6PD activity also increased but it did not reach the control value. However when taurine was administrated (300 mg/kg) the activity of NADPH oxidase reached the control value; furthermore, G6PD activity also increased but it could not reach to the control value. When taurine was administrated alone, no effect on these enzymes was observed. Following the endotoxin administration, the activity of XO considerably increased. When taurine was administrated together with endotoxine and alone, this activity decreased compared to control value in both conditions. These results indicate that the O₂ ^•− formation in PMN leukocytes after the endotoxin administration is ensured by the catalysis of XO due to the inhibited NADPH oxidase activity. It was observed that taurine has considerable anti-inflammatory and antioxidant effects. However, conflicting results were obtained when taurine was administrated alone or together with an oxidant agent.

Keywords: Keywords: Respiratory burst – Polymorphonuclear leukocyte – Taurine – Endotoxemia

Protective effect of gamma-aminobutyric acid (GABA) against cytotoxicity of ethanol in isolated rat hepatocytes involves modulations in cellular polyamine levels by T. Norikura; A. Kojima-Yuasa; D. Opare Kennedy; I. Matsui-Yuasa (pp. 419-423).

Gamma-aminobutyric acid (GABA) is considered to be a multifunctional molecule with various physiological effects throughout the body. It is also evident that the liver contains GABA and its transporter. However, the functions of GABA in liver have not been well documented. In this study, the cytoprotective effect of GABA against ethanol-induced hepatotoxicity was evaluated in primary cultured rat hepatocytes. Addition of ethanol induced decrease of cell viability in a dose-dependent manner. However, treatment with GABA resulted in a dose-dependent recovery from ethanol (150 mM)-induced cytotoxicity.GABA reversed the ethanol-induced decrease in intracellular polyamine levels. Furthermore, the addition of polyamines also reversed the ethanol-induced decrease of cell viability. These results suggest that GABA is protective against the cytotoxicity of ethanol in isolated rat hepatocytes and this effect may be modulated by the maintenance of intracellular polyamine levels.

Keywords: Keywords: GABA – Ethanol – Hepatocytes – Polyamines

Taurine promotes connective tissue growth factor (CTGF) expression in osteoblasts through the ERK signal pathway by L.-Q. Yuan; Y. Lu; X.-H. Luo; H. Xie; X.-P. Wu; E.-Y. Liao (pp. 425-430).

Taurine is found in bone tissue, but its function in skeletal tissue is not fully understood. The present study was undertaken to investigate regulation of gene expression of connective tissue growth factor (CTGF), and the roles of mitogen-activated protein kinases (MAPKs) in murine osteoblast MC3T3-E1 cells treated with taurine. Western blot analysis showed taurine stimulated CTGF protein secretion in a dose- and time-dependent manner. Taurine induced activation of extracellular signal-regulated kinase (ERK), but not p38 and c-jun N-terminal Kinase (JNK), in osteoblasts. Furthermore, pretreatment of osteoblasts with the ERK inhibitor PD98059 abolished the taurine-induced CTGF production. These data indicate that taurine induces CTGF secretion in MC3T3-E1 cells mediated by the ERK pathway, and suggest that osteoblasts are direct targets of taurine.

Keywords: Keywords: Taurine – Osteoblast – Connective tissue growth factor – Mitogen-activated protein kinase

Comparison of in vitro antioxidant and antiradical activities of L-tyrosine and L-Dopa by İ. Gülçin (pp. 431-438).

Phenolic compounds are interesting because of their antioxidant properties. In the present study, the antioxidant properties of L-tyrosine as a monophenolic and L-Dopa as a diphenolic amino acid were investigated by using different antioxidant assays: (i) 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH^•) scavenging; (ii) 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation decolorization assay; (iii) total antioxidant activity by ferric thiocyanate method; (iv) ferric ions (Fe³⁺) reducing power; (v) superoxide anion radical (O₂ ^•−) scavenging; (vi) hydrogen peroxide (H₂O₂) scavenging, and (vii) ferrous ions (Fe²⁺) chelating activities. Butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), α-tocopherol and trolox, a water-soluble analogue of tocopherol, were used as the reference antioxidant compounds. At the same concentration (20 µg/mL), L-tyrosine and L-Dopa showed 30.6 and 67.9% inhibition of lipid peroxidation of linoleic acid emulsion, respectively. On the other hand, BHA, BHT, α-tocopherol and trolox indicated inhibitions of 74.4, 71.2, 54.7 and 20.1% on the peroxidation of linoleic acid emulsion, respectively, at the above-mentioned concentration. In addition, L-tyrosine and L-Dopa had an effect on DPPH radical scavenging, ABTS radical scavenging, superoxide anion radical scavenging, H₂O₂ scavenging, total ferric ions reducing power and metal chelating on ferrous ions activities.

Keywords: Keywords: Antioxidant activity – L-Tyrosine – L-Dopa – Metal chelating – Amino acids – Radical scavenging

Taurine release in mouse brain stem slices under cell-damaging conditions by P. Saransaari; S. S. Oja (pp. 439-446).

Taurine has been thought to be essential for the development and survival of neural cells and to protect them under cell-damaging conditions. In the brain stem taurine regulates many vital functions, including cardiovascular control and arterial blood pressure. We have recently characterized the release of taurine in the adult and developing brain stem under normal conditions. Now we studied the properties of preloaded [³H]taurine release under various cell-damaging conditions (hypoxia, hypoglycemia, ischemia, the presence of metabolic poisons and free radicals) in slices prepared from the mouse brain stem from developing (7-day-old) and young adult (3-month-old) mice, using a superfusion system. Taurine release was greatly enhanced under these cell-damaging conditions, the only exception being the presence of free radicals in both age groups. The ischemia-induced release was characterized to consist of both Ca²⁺-dependent and -independent components. Moreover, the release was mediated by Na⁺-, Cl⁻-dependent transporters operating outwards, particularly in the immature brain stem. Cl⁻ channel antagonists reduced the release at both ages, indicating that a part of the release occurs through ion channels, and protein kinase C appeared to be involved. The release was also modulated by cyclic GMP second messenger systems, since inhibitors of soluble guanylyl cyclase and phosphodiesterases suppressed ischemic taurine release. The inhibition of phospholipases also reduced taurine release at both ages. This ischemia-induced taurine release could constitute an important mechanism against excitotoxicity, protecting the brain stem under cell-damaging conditions.

Keywords: Keywords: Taurine release – Cell-damaging conditions – Ischemia – Ion channel inhibitors – Second messengers – Ca²⁺-dependency – Brain stem slices – Adult and developing mice

Comparison of taurine chloramine and taurine bromamine effects on rheumatoid arthritis synoviocytes by E. Kontny; M. Chorąży-Massalska; W. Rudnicka; J. Marcinkiewicz; W. Maśliński (pp. 447-452).

Fibroblast-like synoviocytes (FLS) participate in rheumatoid arthritis (RA) chronic synovitis by producing pro-inflammatory cytokines (IL-6, IL-8), growth factors (VEGF) and other inflammatory mediators (PGE₂, NO). We have previously reported that Tau-Cl, generated by neutrophils, inhibits in vitro some of these pathogenic RA FLS functions. Taurine bromamine (Tau-Br) originates from eosinophils and neutrophils, and its immunoregulatory activities are poorly known. Therefore, we investigated the effects of Tau-Br on RA FLS functions and compared it to Tau-Cl anti-inflammatory action. When applied at noncytotoxic concentrations: (i) Tau-Br inhibited IL-6 and PGE₂ production with potency similar to Tau-Cl (IC₅₀ ≈ 250 µM), (ii) Tau-Br failed to affect VEGF and IL-8 synthesis, while Tau-Cl exerted inhibitory effect (IC₅₀ ≈ 400 µM), (iii) none of these compounds affected NO generation and iNOS expression. Thus, Tau-Cl is more effective than Tau-Br in normalization of pro-inflammatory RA FLS functions.

Keywords: Keywords: Taurine chloramine – Taurine bromamine – Inflammation – Rheumatoid arthritis – Synoviocytes

The effect of tryptophan administration on ileum contractility and oxidant status in mice by Ç. Özer; B. Gönül; Z. S. Ercan; G. Take; D. Erdoğan (pp. 453-458).

L-Tryptophan (TRP) is the precursor amino acid for the synthesis of serotonin (5-HT). 5-HT is effective both on the food intake and gastrointestinal system contractility. The aim of this study was to search the effects of systemic TRP treatment on 5-HT levels of ileum and searching the effect of ileal contractility and oxidant status. Swiss-albino mice were divided into two groups: 1. Control, 2. TRP-treated (100 mg/kg/24 h, i.p., for 7 days). Body weights were recorded at the beginning and at the end of experiments. Acetylcholine-induced contractile responses in the isolated ileum were recorded on polygraph. Ileal tissue malondialdehyde and glutathione levels determined by spectrophotometric and ileal tissue 5-HT levels were measured by immunohistochemical methods. TRP treatment decreased body weight and increased ileal contractile response. In the TRP-treated group, ileum malondialdehyde levels increased and glutathione levels decreased. Immunohistochemical detection showed that ileal 5-HT levels were increased by TRP treatment. There is a relationship between increased oxidative stress and increased contractility in the ileal tissue of the TRP-treated animals. These effects may be related to increased ileal 5-HT synthesis.

Keywords: Keywords: Tryptophan – Serotonin – Ileal contractility – Oxidant status – Immunohistochemistry

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Amino Acids: The Forum for Amino Acid, Peptide and Protein Research (v.32, #3)