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Amino Acids: The Forum for Amino Acid, Peptide and Protein Research (v.34, #1)

Structural diversity of bicyclic amino acids by A. Trabocchi; D. Scarpi; A. Guarna (pp. 1-24).

Over the years biomedical research has been constantly oriented towards the development of new therapeutics based on bioactive peptides and their analogues. In particular, the generation of compounds having structures and functions similar to bioactive peptides, named “peptidomimetics”, raised much interest among organic and medicinal chemists due to the possibility by using such compounds to improve both potency and stability of peptidic lead compounds. In the context of this research area, unnatural amino acids are of great interest in drug discovery, and their use as new building blocks for the development of peptidomimetics with high diversity level and possessing high-ordered structures is of special interest. In particular, medicinal chemistry has taken advantage of the use of amino acid homologues and of cyclic and polycyclic templates to introduce elements of diversity for the generation of new molecules as drug candidates. Bicyclic amino acids have been developed as reverse turn mimetics and dipeptide isosteres, and the constraint imposed by their structures has been reported as a tool for controlling the conformational preferences of modified peptides. Moreover, synthetic efforts have been driven to the generation of diverse structures based on the modulation of ring size and scaffold decoration by suitable functional groups. Herein is reported an overview of different classes of bicyclic amino acids, taking into account the strategies to achieve structurally diverse templates, and some implications in medicinal chemistry are also disclosed.

Keywords: Keywords: Scaffold – Peptide – Peptidomimetic – Drug design

Differences in amino acids composition and coupling patterns between mesophilic and thermophilic proteins by X.-X. Zhou; Y.-B. Wang; Y.-J. Pan; W.-F. Li (pp. 25-33).

Thermophilic proteins show substantially higher intrinsic thermal stability than their mesophilic counterparts. Amino acid composition is believed to alter the intrinsic stability of proteins. Several investigations and mutagenesis experiment have been carried out to understand the amino acid composition for the thermostability of proteins. This review presents some generalized features of amino acid composition found in thermophilic proteins, including an increase in residue hydrophobicity, a decrease in uncharged polar residues, an increase in charged residues, an increase in aromatic residues, certain amino acid coupling patterns and amino acid preferences for thermophilic proteins. The differences of amino acids composition between thermophilic and mesophilic proteins are related to some properties of amino acids. These features provide guidelines for engineering mesophilic protein to thermophilic protein.

Keywords: Keywords: Thermophilic protein – Thermostability – Amino acid composition – Amino acid coupling pattern

Polyamines and abiotic stress: recent advances by M. D. Groppa; M. P. Benavides (pp. 35-45).

In this review we will concentrate in the results published the last years regarding the involvement of polyamines in the plant responses to abiotic stresses, most remarkably on salt and drought stress. We will also turn to other types of abiotic stresses, less studied in relation to polyamine metabolism, such as mineral deficiencies, chilling, wounding, heavy metals, UV, ozone and paraquat, where polyamine metabolism is also modified.There is a great amount of data demonstrating that under many types of abiotic stresses, an accumulation of the three main polyamines putrescine, spermidine and spermine does occur. However, there are still many doubts concerning the role that polyamines play in stress tolerance. Several environmental challenges (osmotic stress, salinity, ozone, UV) are shown to induce ADC activity more than ODC. The rise in Put is mainly attributed to the increase in ADC activity as a consequence of the activation of ADC genes and their mRNA levels. On the other hand, free radicals are now accepted as important mediators of tissue injury and cell death. The polycationic nature of polyamines, positively charged at physiological pH, has attracted the attention of researchers and has led to the hypothesis that polyamines could affect physiological systems by binding to anionic sites, such as those associated with nucleic acids and membrane phospholipids. These amines, involved with the control of numerous cellular functions, including free radical scavenger and antioxidant activity, have been found to confer protection from abiotic stresses but their mode of action is not fully understood yet. In this review, we will also summarize information about the involvement of polyamines as antioxidants against the potential abiotic stress-derived oxidative damage.

Keywords: Keywords: Antioxidants – Polyamines – Abiotic stress – Stress tolerance

α-Amino acid behaves differently from β- or γ-amino acids as treated by trimetaphosphate by X. Gao; Y. Liu; P. X. Xu; Y. M. Cai; Y. F. Zhao (pp. 47-53).

The condensation reactions of sodium trimetaphosphate with single amino acids, namely glycine, L-alanine, β-alanine and γ-aminobutyric acid or pairs of these amino acids were reinvestigated by electrospray ion-trap mass spectrometry and high performance liquid chromatography. It was found when mixtures were treated by sodium trimetaphosphate only in the presence of α-amino acid dipeptides were formed. Without addition of α-amino acids, the β-amino acid or γ-aminobutyric acid could not form peptide either by themselves or with their mixtures under the same conditions. From the data it is concluded that phosphate might select α-amino acids to produce the peptides being important precursors for the origin of life.

Keywords: Keywords: Trimetaphosphate – α-Amino acids – β-Amino acids – γ-Amino acids – Peptide – LC-ESI-MS

Relationships between the sedative and hypnotic effects of intracerebroventricular administration of L-serine and its metabolites, pyruvate and the derivative amino acids contents in the neonatal chicks under acute stressful conditions by M. Asechi; I. Kurauchi; S. Tomonaga; H. Yamane; R. Suenaga; Y. Tsuneyoshi; D. M. Denbow; M. Furuse (pp. 55-60).

Intracerebroventricular (i.c.v.) injection of L-serine was shown to have sedative and hypnotic effects on neonatal chicks under acute stressful conditions. To clarify the central mechanism of these effects of L-serine, two experiments were done. First, we focused on the glycogenic pathway in which L-serine is converted into pyruvate and finally glucose. I.c.v. administration of pyruvate (0.84 µmol) did not induce any behavioral and endocrinological changes, while L-serine and glucose triggered sedative and hypnotic effects. Secondly, the relationship between the sedation by L-serine and the metabolism into other amino acids which have sedative effects was investigated in the telencephalon and diencephalon. In both brain areas, a dose-dependent increase was seen in L-serine, although other amino acids were not changed. In the present study, it was concluded that the sedative action of L-serine was not due to the action of its metabolite pyruvate, or to the action of other amino acids.

Keywords: Keywords: L-serine – Pyruvate – Intracerebroventricular injection – Social separation stress – Amino acids contents

Kinetics of the photosensitized oxidation of chymotrypsin in different media by E. Reynoso; M. A. Biasutti; N. A. García (pp. 61-68).

The kinetic aspects of the Perinaphthenone-sensitized photooxidation (singlet molecular oxygen [O₂ (¹Δ_g)]-mediated) of α-chymotrypsin (α-Chymo) have been studied at pH 8 and pH 11 as well in reverse micelles (RMs) of sodium 1, 4 bis (2-ethylhexyl) sulfosuccinate (AOT) in n-heptane.The rate constant values for both overall (k_t) and chemical (k_r) quenching of O₂ (¹Δ_g) by α-Chymo in homogeneous media were higher at pH = 11 than at pH = 8, indicating that the OH-ionized tyrosine (Tyr) residues, clearly dominate the quenching process. Besides, the rate constants in water were higher than those determined in RMs, demonstrating that the organized medium protects the protein against photooxidation, probably due to a diminution in both, the accessibility towards oxidizable amino acid residues and the polarity inside the aggregate, as compared to water. The protection effect of α-Chymo against the attack by the oxidative species O₂ (¹Δ_g) in RMs of AOT seems to be due to the increase of protein stability by the encapsulation within the micellar structure.The effect of both, surfactant concentration and variation of the ratio ([H₂O]/[AOT]) = W on the reactive rate constant was also investigated. The process does not depend significantly on micelles concentration while the k_r values increase as W increases. Furthermore, at W = 30, the highest W studied, k_r tends to the value obtained in aqueous medium.

Keywords: Keywords: AOT – α-Chymotrypsin – Photooxidation – Reverse micelles – Singlet molecular oxygen

High-throughput capillary electrophoresis method for plasma cysteinylglycine measurement: evidences for a clinical application by A. Zinellu; A. Pinna; E. Zinellu; S. Sotgia; L. Deiana; C. Carru (pp. 69-74).

Increased levels in plasma homocysteine and cysteine, and more recently, decreased levels in cysteinylglycine have been indicated as a risk factor for vascular diseases. Most assays focused their attention only on homocysteine determination and when also other thiols were measured, analytical times drastically increased. By modifying our previous method for thiols detection, we set up a rapid capillary electrophoresis method for the selective quantification of plasma cysteinylglycine, cutting the analysis time of about 50%. Samples were treated with tri-n-butylphosphine as reducing agent, proteins were precipitated with trichloroacetic acid and released thiols were successively derivatized by the selective thiol laser-induced fluorescence-labeling agent 5-iodoacetamidofluorescein and separated by capillary electrophoresis. A baseline separation between peaks was obtained in about 2 min using 3 mmol/L sodium phosphate/2.5 mmol/L boric acid as electrolyte solution with 75 mmol/L N-methyl-D-glucamine at pH 11.25 in a 47 cm long capillary with a cartridge temperature of 45 °C. The method application was checked by measuring plasma Cys-Gly levels in a group of patients affected by retinal vein occlusion (RVO), an important cause of visual loss in the elderly. The low levels of Cys-Gly found in the RVO patients suggest that these small thiols may have importance in the disease development.

Keywords: Keywords: Cysteinylglycine – Cysteine – Homocysteine – Capillary electrophoresis – Retinal vein occlusion

Taurine release in developing mouse hippocampus is modulated by glutathione and glutathione derivatives by R. Janáky; C. A. Shaw; S. S. Oja; P. Saransaari (pp. 75-80).

Glutathione (reduced form GSH and oxidized form GSSG) constitutes an important defense against oxidative stress in the brain, and taurine is an inhibitory neuromodulator particularly in the developing brain. The effects of GSH and GSSG and glycylglycine, γ-glutamylcysteine, cysteinylglycine, glycine and cysteine on the release of [³H]taurine evoked by K⁺-depolarization or the ionotropic glutamate receptor agonists glutamate, kainate, 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate (NMDA) were now studied in slices from the hippocampi from 7-day-old mouse pups in a perfusion system. All stimulatory agents (50 mM K⁺, 1 mM glutamate, 0.1 mM kainate, 0.1 mM AMPA and 0.1 mM NMDA) evoked taurine release in a receptor-mediated manner. Both GSH and GSSG significantly inhibited the release evoked by 50 mM K⁺. The release induced by AMPA and glutamate was also inhibited, while the kainate-evoked release was significantly activated by both GSH and GSSG. The NMDA-evoked release proved the most sensitive to modulation: L-Cysteine and glycine enhanced the release in a concentration-dependent manner, whereas GSH and GSSG were inhibitory at low (0.1 mM) but not at higher (1 or 10 mM) concentrations. The release evoked by 0.1 mM AMPA was inhibited by γ-glutamylcysteine and cysteinylglycine, whereas glycylglycine had no effect. The 0.1 mM NMDA-evoked release was inhibited by glycylglycine and γ-glutamylcysteine. In turn, cysteinylglycine inhibited the NMDA-evoked release at 0.1 mM, but was inactive at 1 mM. Glutathione exhibited both enhancing and attenuating effects on taurine release, depending on the glutathione concentration and on the agonist used. Both glutathione and taurine act as endogenous neuroprotective effectors during early postnatal life.

Keywords: Keywords: Glutathione – Glutathione derivatives – Taurine release – Neuroplasticity – Hippocampal slices – Developing mice

Prediction of mutations engineered by randomness in H5N1 neuraminidases from influenza A virus by G. Wu; S. Yan (pp. 81-90).

In this proof-of-concept study, we attempt to determine whether the cause-mutation relationship defined by randomness is protein dependent by predicting mutations in H5N1 neuraminidases from influenza A virus, because we have recently conducted several concept-initiated studies on the prediction of mutations in hemagglutinins from influenza A virus. In our concept-initiated studies, we defined the randomness as a cause for mutation, upon which we built a cause-mutation relationship, which is then switched into the classification problem because the occurrence and non-occurrence of mutations can be classified as unity and zero. Thereafter, we used the logistic regression and neural network to solve this classification problem to predict the mutation positions in hemagglutinins, and then used the amino acid mutating probability to predict the would-be-mutated amino acids. As the previous results were promising, we extend this approach to other proteins, such as H5N1 neuraminidase in this study, and further address various issues raised during the development of this approach. The result of this study confirms that we can use this cause-mutation relationship to predict the mutations in H5N1 neuraminidases.

Keywords: Keywords: Influenza – Logistic regression – Mutation – Neuraminidase – Prediction

Expression profiles of the genes associated with metabolism and transport of amino acids and their derivatives in rat liver regeneration by C. S. Xu; C. F. Chang (pp. 91-102).

Amino acids (AA) are components of protein and precursors of many important biological molecules. To address effects of the genes associated with metabolism and transport of AA and their derivatives during rat liver regeneration (LR), we firstly obtained the above genes by collecting databases data and retrieving related thesis, and then analyzed their expression profiles during LR using Rat Genome 230 2.0 array. The LR-associated genes were identified by comparing the gene expression difference between partial hepatectomy (PH) and sham-operation (SO) rat livers. It was approved that 134 genes associated with metabolism of AA and their derivatives and 26 genes involved in transport of them were LR-associated. The initially and totally expressing number of these genes occurring in initial phase of LR (0.5–4 h after PH), G0/G1 (4–6 h after PH), cell proliferation (6–66 h after PH), cell differentiation and structure-function reconstruction of liver tissue (72–168 h after PH) were respectively 76, 17, 79, 5 and 162, 89, 564, 195, illustrating that these LR-associated genes were initially expressed mainly in initial stage, and functioned in different phases. Frequencies of up-regulation and down-regulation of them being separately 564 and 357 demonstrated that genes up-regulated outnumbered those down-regulated. Categorization of their expression patterns into 22 types implied the diversity of cell physiological and biochemical activities. According to expression changes and patterns of the above-mentioned genes in LR, it was presumed that histidine biosynthesis in the metaphase and anaphase, valine metabolism in the anaphase, and metabolism of glutamate, glutamine, asparate, asparagine, methionine, alanine, leucine and aromatic amino acid almost were enhanced in the whole LR; as for amino acid derivatives, transport of neutral amino acids, urea, γ-aminobutyric acid, betaine and taurine, metabolism of dopamine, heme, S-adenosylmethionine, thyroxine, and biosynthesis of hydroxyproline, nitric oxide, orinithine, polyamine, carnitine, selenocysteine were augmented during the entire liver restoration. Above results showed that metabolism and transport of AA and their derivates were necessary in liver regeneration.

Keywords: Keywords: Partial hepatectomy – Rat genome 230 2.0 array – Metabolism and transport of amino acids and their derivatives – Genes associated with liver regeneration

Predicting DNA-binding proteins: approached from Chou’s pseudo amino acid composition and other specific sequence features by Y. Fang; Y. Guo; Y. Feng; M. Li (pp. 103-109).

DNA-binding proteins play a pivotal role in gene regulation. It is vitally important to develop an automated and efficient method for timely identification of novel DNA-binding proteins. In this study, we proposed a method based on alone the primary sequences of proteins to predict the DNA-binding proteins. DNA-binding proteins were encoded by autocross-covariance transform, pseudo-amino acid composition, dipeptide composition, respectively and also the different combinations of the three encoded methods; further, these feature matrices were applied to support vector machine classifiers to predict the DNA-binding proteins. All modules were trained and validated by the jackknife cross-validation test. Through comparing the performance of these substituted modules, the best result was obtained from pseudo-amino acid composition with the overall accuracy of 96.6% and the sensitivity of 90.7%. The results suggest that it can efficiently predict the novel DNA-binding proteins only using the primary sequences.

Keywords: Keywords: DNA-binding proteins – Autocross-covariance transform – Pseudo-amino acid composition – Dipeptide composition – Support vector machine

Using pseudo amino acid composition to predict transmembrane regions in protein: cellular automata and Lempel-Ziv complexity by Y. Diao; D. Ma; Z. Wen; J. Yin; J. Xiang; M. Li (pp. 111-117).

Transmembrane (TM) proteins represent about 20–30% of the protein sequences in higher eukaryotes, playing important roles across a range of cellular functions. Moreover, knowledge about topology of these proteins often provides crucial hints toward their function. Due to the difficulties in experimental structure determinations of TM protein, theoretical prediction methods are highly preferred in identifying the topology of newly found ones according to their primary sequences, useful in both basic research and drug discovery. In this paper, based on the concept of pseudo amino acid composition (PseAA) that can incorporate sequence-order information of a protein sequence so as to remarkably enhance the power of discrete models (Chou, K. C., Proteins: Structure, Function, and Genetics, 2001, 43: 246–255), cellular automata and Lempel-Ziv complexity are introduced to predict the TM regions of integral membrane proteins including both α-helical and β-barrel membrane proteins, validated by jackknife test. The result thus obtained is quite promising, which indicates that the current approach might be a quite potential high throughput tool in the post-genomic era. The source code and dataset are available for academic users at liml@scu.edu.cn.

Keywords: Keywords: Cellular automata – Pseudo amino acid composition – Lempel-Ziv complexity – Augmented covariant-discriminant algorithm – Chou’s invariance theorem – Transmembrane regions

Using pseudo amino acid composition to predict protein subnuclear location with improved hybrid approach by F.-M. Li; Q.-Z. Li (pp. 119-125).

The subnuclear localization of nuclear protein is very important for in-depth understanding of the construction and function of the nucleus. Based on the amino acid and pseudo amino acid composition (PseAA) as originally introduced by K. C. Chou can incorporate much more information of a protein sequence than the classical amino acid composition so as to significantly enhance the power of using a discrete model to predict various attributes of a protein, an algorithm of increment of diversity combined with the improved quadratic discriminant analysis is proposed to predict the protein subnuclear location. The overall predictive success rates and correlation coefficient are 75.4% and 0.629 for 504 single localization proteins in jackknife test, and 80.4% for an independent set of 92 multi-localization proteins, respectively. For 406 single localization nuclear proteins with ≤25% sequence identity, the results of jackknife test show that the overall accuracy of prediction is 77.1%.

Keywords: Keywords: Subnuclear localization – Increment of diversity – Quadratic discriminant – Covariant discriminant function – Chou’s pseudo amino acid composition

A MBP-FAAH fusion protein as a tool to produce human and rat fatty acid amide hydrolase: expression and pharmacological comparison by G. Labar; F. V. Vliet; J. Wouters; D. M. Lambert (pp. 127-133).

Fatty acid amide hydrolase (FAAH), a membrane-anchored enzyme responsible for the termination of endocannabinoid signalling, is an attractive target for treating conditions such as pain and anxiety. Inhibitors of the enzyme, optimized using rodent FAAH, are known but their pharmacology and medicinal chemistry properties on the human FAAH are missing. Therefore recombinant human enzyme would represent a powerful tool to evaluate new drug candidates. However, the production of high amounts of enzyme is hampered by the known refractiveness of FAAH to overexpression. Here, we report the successful overexpression of rat and human FAAH as a fusion to the E. coli maltose-binding protein, retaining catalytic properties of native FAAH. Several known FAAH inhibitors were tested and differences in their potencies toward the human and rat FAAH were found, underscoring the importance of using a human FAAH in the development of inhibitors.

Keywords: Keywords: Fatty acid amide hydrolase – Endocannabinoid system – Protein overexpression – Fusion proteins – Inhibitors characterization – Maltose-binding protein

Protective effect of oxidative stress in HaCaT keratinocytes expressing E7 oncogene by J.-H. Shim; K.-H. Kim; Y.-S. Cho; H.-S. Choi; E. Y. Song; P.-K. Myung; J. S. Kang; S.-K. Suh; S. N. Park; D.-Y. Yoon (pp. 135-141).

In a previous study, we established a stable cell line which constitutively expresses E7 in HaCaT human keratinocyte cell line and identified various relevant factors including oxygen modulators affected by the E7 oncogene. E7-expressing HaCaT cells (HaCaT/E7) appeared to be more resistant to H₂O₂-induced cell death. Here, we demonstrate how E7 oncogene would modulate oxidative stress-induced cell death. In addition, we verified the increased expression of catalase in the HaCaT/E7 by Western blot analysis. The results suggest that the E7 oncogene would induce higher resistance to ROS-induced cell injury in the E7-infected cells via the upregulation of catalase. To investigate these paradoxical effects of high concentrations of H₂O₂ (500 µM–1 mM), we examined their effects on receptor mediated apoptosis, cell death via the mitochondrial pathway and modulation of apoptosis related factors. Our results revealed that HaCaT keratinocytes infected with HPV 16 E7 oncogene modulated expressions of catalase, Bcl-xL, IL-18, Fas, Bad, and cytochrome c as well as NF-κB, resulting in the resistance to oxidative stress-induced cell death.

Keywords: Keywords: Human papillomavirus – E7 – Apoptosis signal

Stress response and changes in amino acid requirements in Senegalese sole (Solea senegalensis Kaup 1858) by C. Aragão; J. Corte-Real; B. Costas; M. T. Dinis; L. E. C. Conceição (pp. 143-148).

Fish in aquaculture are often exposed to various stressors that may change their ability to survive or limit growth. Amino acids are used for processes other than growth, including stress response. This study intended to analyse how repeated acute handling stress can affect growth and amino acid requirements in fish. Senegalese sole juveniles were weekly held in the air during 3 min (Handling) for 9 weeks; Control groups were left undisturbed. Growth and plasma levels of stress indicators and of free amino acids were assessed at the end of the experiment. Plasma cortisol and osmolality levels showed that fish in the Handling treatment were stressed, but growth was unaffected. Plasma amino acid concentrations indicate that their requirements in stressed fish were altered, which probably reflects the synthesis of proteins or other specific compounds related to stress response.

Keywords: Keywords: Handling stress – Cortisol – Osmolality – Amino acids – Requirements – Solea senegalensis

Application of several types of substrates to ficin-catalyzed peptide synthesis by H. Sekizaki; E. Toyota; T. Fuchise; S. Zhou; Y. Noguchi; K. Horita (pp. 149-153).

The capability of ficin, a cystine protease, to form peptide bonds was investigated using several types of N-Boc-amino acid phenyl and naphthyl esters as acyl donor components. Enzyme-catalyzed peptide synthesis was carried out under optimized reaction conditions of pH, acyl acceptor concentration and selection of the best yield organic solvent. It used a condensation of N-Boc-Ala-OpGu and Ala-pNA as a model reaction. The products were obtained in 72–96% yield using 10 different substrates, within a few minutes of reaction time.

Keywords: Keywords: N-Boc-Amino acid – Amidinophenyl esters – Guanidinophenyl esters – (Guanidinomethyl)phenyl ester – Guanidinonaphthyl ester – Enzymatic peptide synthesis – Ficin

Cloning and expression analysis of YY1AP-related protein in the rat brain by T. Ohtomo; T. Horii; M. Nomizu; T. Suga; J. Yamada (pp. 155-161).

YY1AP-related protein (YARP) is a structural homolog of YY1AP, a transcriptional coactivator of the multifunctional transcription factor YY1. We cloned a rat YARP cDNA that encoded a 2256 amino acid protein with 93% homology to the human counterpart. Northern blots revealed significant expression of the YARP gene in the rat brain. In situ hybridization demonstrated its expression in neurons throughout the brain, including pyramidal cells in the cerebral cortex and hippocampus and granule cells in the dentate gyrus. YARP was coexpressed with YY1 in these same neuronal cells. However, there was no evidence of YARP expression in glia. In the developing rat brain, the level of YARP mRNA (∼10 kb) peaked at embryonic day 18 and promptly declined thereafter to reach the steady-state level found in adulthood, by 14 days after birth. These results suggest that YARP functions at a late stage of neurogenesis during perinatal development of the rat brain, as well as in mature neurons.

Keywords: Keywords: YY1-associated protein – YARP – Dingo – GON4L – Transcriptional coactivator – Neuron

1-(N-chloroacetylamino)-alkylphosphonic acids – synthetic precursors of phosphonopeptides by Z. H. Kudzin; R. Depczyński; M. H. Kudzin; J. Drabowicz (pp. 163-168).

General procedures of N-chloroacetylation of the representative 1-aminoalkylphosphonic acids (Gly^P, Ala^P, Val^P, Pgly^P and Phe^P) are described. These 1-(N-chloroacetylamino)-alkylphosphonic acids were converted into the corresponding glycylphosphonodipeptides (Gly-AA^P) and/or related N-alkylglycylphosphonodipeptides (Me_nGly-AA^P) in the course of ammonolysis/aminolysis. Physico-chemical properties of synthesized 1-(N-chloroacetylamino)-alkylphosphonic acids and phosphonodipeptides are characterized.

Keywords: Keywords: Aminophosphonic acids – N-chloroacetylation – Ammonolysis – Aminolysis – Phosphonopeptides – Peptidomimetics

Taurine reduces caspase-8 and caspase-9 expression induced by ischemia in the mouse hypothalamic nuclei by A. G. Taranukhin; E. Y. Taranukhina; P. Saransaari; I. M. Djatchkova; M. Pelto-Huikko; S. S. Oja (pp. 169-174).

Taurine is a sulphur-containing amino acid abundant in the nervous system. It protects cells from ischemia-induced apoptosis, but the mechanism underlying this is not well established. The aim of our study was to explore the effects of taurine on two main pathways of apoptosis induced by ischemia: receptor-mediated and mitochondrial cell death. Brain slices containing the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus were incubated in vitro under control and simulated ischemic (oxygen-glucose deprivation for 30 min) conditions in the absence and presence of 20 mM taurine. Brain slices were harvested after the 180-min “postischemic” period and fixed in 4% paraformaldehyde. To estimate apoptosis, immunostaining was done for caspase-8 and caspase-9 in paraffin-embedded sections. Immunoreactive caspase-8 and caspase-9 cells were observed in SON and PVN in all experimental groups, but in the “ischemic” group the expression of caspase-8 and caspase-9 and the number of immunoreactive cells was significantly increased in both hypothalamic nuclei. Addition of taurine (20 mM) to the incubation medium induced a marked decrease in caspase-8 and caspase-9 immunoreactivity after ischemia in SON and PVN when compared with the taurine-untreated “ischemic” group. Taurine reduces ischemia-induced caspase-8 and caspase-9 expression, the key inductors of apoptosis in SON and PVN.

Keywords: Keywords: Taurine – Ischemia – Caspase-8 – Caspase-9 – Hypothalamus – Brain slices – Mice

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Amino Acids: The Forum for Amino Acid, Peptide and Protein Research (v.34, #1)