Physiological roles of glutathione in organism

Glutation (γ-glutamil-cisteinilglicin, GSH) je tripeptid prisutan u velikim količinama u svim stanicama sisavaca. Sintetizira se u stanicama svih organa, posebno u jetri. Najveća količina nalazi se u citosolu, mitohondriju i ER. Služi kao antioksidans i detoksifikator u mnogim procesima metabolizma i regulira stanična zbivanja. Postoji u dva oblika-reduciranom (GSH) koji može oksidirati do disulfida (GSSG), a njihov omjer određuje redoks stanje stanice koje je bitan posrednik u više procesa. U ovom radu obrađuju se uloge GSH kao regulatora staničnog redoks statusa u kontroli transkripcijskih faktora i imunološkog odgovora te kao kofaktora u sintezi proupalnih posrednika ili spoja s NO. Smanjenje razine GSH u uvjetima oksidacijskog stresa aktivira transkripcijske faktore NF-κB i AP-1 koji potiču ekspresiju mnogih proupalnih gena i gena za citokine. U imunološkom sustavu GSH ima dvojaku ulogu: utječe na smanjenje sinteze citokina koji mogu dodatno pojačati oksidacijski stres, a dovoljna količina GSH potrebna je za proliferaciju limfocita T i odgovarajući imunološki odgovor. GSH služi i kao kofaktor u pojedinim koracima sinteze proupalnih posrednika, leukotriena i prostaglandina, koje kataliziraju membranski enzimi porodice GSH S-transferaza imena MAPEG. NO se može spojiti s GSH pri čemu nastaje S-nitrozoglutation (GSNO) koji može posttranslacijskom modifikacijom preko S-tiolacije ili S-glutationilacije utjecati na aktivnost proteina i time inhibirati apoptozu ili utjecati na redoks stanje stanice.Glutathione (γ-glutamylcysteinylglycine, GSH) is a tripeptid present in large levels in all mammalian tissues. It is synthetized within the cells of all organs, especially in the liver. The largest levels of GSH are present in cytosol, mitochondria and ER. GSH serves as antioxidant, detoxifying agent in a number of metabolism processes and it modulates cell events. There are two forms of GSH: reduced form (GSH) which can oxidize to disulphide (GSSG), GSH/GSSG ratio determines redox state of cells which is important factor in many processes. This review explaines roles of GSH as a regulator of cellular processes in a modulation of transcriptional factors and immune responses and, also, as a cofactor in proinflammatory mediators synthesis and NO-adduct formation. In conditions of oxidative stress, a decrease in GSH levels activates transcriptional factors NF-κB i AP-1 which then activate pro-inflammatory genes and cytokine genes expression. GSH has a double role in the immune system: it affects the decrease in cytokine synthesis which can enhance oxidative stress and, also, adequate levels of GSH are essential for T lymphocyte proliferation and successful immune response. In the synthesis of pro-inflammatory mediators, leukotrienes and prostaglandins, GSH serves as a cofactor in some of the steps catalyzed by special GSH-S transferase membrane-bound enzymes called MAPEG. NO can form an adduct with GSH forming S-nitrosoglutathione (GSNO) which by posttranslational modification through Sthiolation and S-glutathionilation can modify protein activity and additionally apoptosis inhibition or cell redox state

Glutationilacija – regulacijska uloga glutationa u fiziološkim procesima

Glutathione (γ-glutamyl-cysteinyl-glycine) is an intracellular thiol molecule and a potent antioxidant that participates in the toxic metabolism phase II biotransformation of xenobiotics. It can bind to a variety of proteins in a process known as glutathionylation. Protein glutathionylation is now recognised as one of important posttranslational regulatory mechanisms in cell and tissue physiology. Direct and indirect regulatory roles in physiological processes include glutathionylation of major transcriptional factors, eicosanoids, cytokines, and nitric oxide (NO). This review looks into these regulatory mechanisms through examples of glutathione regulation in apoptosis, vascularisation, metabolic processes, mitochondrial integrity, immune system, and neural physiology. The focus is on the physiological roles of glutathione beyond biotransformational metabolism.Glutation (γ-glutamil-cisteinil-glicin) stanični je tripeptid, tiolni spoj i jaki antioksidans koji sudjeluje u metabolizmu otrova i biotransformaciji ksenobiotika faze II. Može se vezati na različite proteine u procesu poznatom pod nazivom glutationilacija. Proteinska glutationilacija dokazano je jedan od važnih posttranslacijskih upravljačkih mehanizama u fiziologiji stanica i tkiva. Izravne i neizravne upravljačke uloge u fiziološkim procesima uključuju glutationilaciju glavnih transkripcijskih faktora, eikozanoida, citokina i dušikova oksida (NO). U ovom se preglednom radu razmatraju navedeni upravljački mehanizmi na primjerima regulacije glutationom u apoptozi, vaskularizaciji, metaboličkim procesima, mitohondrijskom integritetu, imunološkom sustavu i fiziologiji živčanog sustava. Težište je rada na novim opisanim fiziološkim ulogama glutationa, pored uobičajeno opisane uloge u biotransformacijskom metabolizmu

Opportunities and Challenges in the Development of Cathode Materials for Rechargeable Mg Batteries

Recent years have seen an intense and renewed interest in the Mg battery research, naming Mg-S the ≫Holy Grail≪ battery, and expectations that Mg battery system will be able to compete and surpass Li-ion batteries in a matter of years. Considerable progress has been achieved in the field of Mg electrolytes, where several new electrolytes with improved electrochemical performance and favorable chemical properties (non-corrosive, non-nucleophilic) were synthesized. Development in the field of cathodes remains a bit more elusive, with inorganic, sulfur, and organic cathodes all showing their upsides and downsides. This review highlights the recent progress in the field of Mg battery cathodes, paying a special attention to the performance and comparison of the different types of the cathodes. It also aims to define advantages and key challenges in the development of each type of cathodes and finally specific questions that should be addressed in the future research

Characterization of the Torsional Piezoelectric-like Response of Tantalum Trisulfide Associated with Charge-Density-Wave Depinning

We have studied the frequency and voltage dependence of voltage-induced torsional strains in orthorhombic TaS3 [V. Ya. Pokrovskii, et al, Phys. Rev. Lett. 98, 206404 (2007)] by measuring the modulation of the resonant frequency of an RF cavity containing the sample. The strain has an onset voltage below the charge-density-wave (CDW) threshold voltages associated with changes in shear compliance and resistance, suggesting that the strain is associated with polarization of the CDW rather than CDW current. Measurements with square-wave voltages show that the strain is very sluggish, not even reaching its dc value at a frequency of 0.1 Hz, but the dynamics appear to be very sample dependent. By applying oscillating torque while biasing the sample with a dc current, we have also looked for strain induced voltage in the sample; none is observed at the low biases where the voltage-induced strains first occur, but an induced voltage is observed at higher biases, probably associated with strain-dependent CDW conductance.Comment: 11 pages, including 3 figures, to be published in Phys. Rev. B (Rapid Comm.

The Dual Nature of the Antiepileptic Drug Valproic Acid, With Possible Beneficial Effects in Alzheimer’s Disease

Valproic acid (VPA) is a short fatty acid with strong anticonvulsant properties. It has diverse effects in different tissues with opposing mechanisms of physiological action. Due to the effects on energy, fatty acid, and cholesterol metabolism, it may be a risk factor for the development of diabetes with its associated complications of atherosclerosis, weight gain, hypertension, insulin resistance and other complications. Its negative effects on the endocrine system can have severe health consequences, especially in the female population.VPA produces proinflammatory and proapoptotic effects in the liver and anti-inflammatory and antiapoptotic effects in the central nervous system. It also causes abnormalities in lipid and cholesterol transport in the liver and the reproductive organs, while in neural stem cells it decreases cholesterol accumulation and helps neural growth and differentiation. However, in the CNS it has some beneficial effects which are proposed to be important in Alzheimer’s disease (AD). In AD mouse models, VPA exerted antiapoptotic effects and the expression of transcription factors that promote neurite growth. Most of the adverse pathogenic actions or beneficial molecular effects are not fully understood. We present an overview and comparison of the different properties of VPA and their effects on estrogen and cholesterol metabolism, lipid transport, Alzheimer’s disease, and on the physiology of the liver, reproductive organs, and neuronsfrom in vitro and in vivo (in animal models and patients) studies

Physiological roles of glutathione in organism

Glutation (γ-glutamil-cisteinilglicin, GSH) je tripeptid prisutan u velikim količinama u svim stanicama sisavaca. Sintetizira se u stanicama svih organa, posebno u jetri. Najveća količina nalazi se u citosolu, mitohondriju i ER. Služi kao antioksidans i detoksifikator u mnogim procesima metabolizma i regulira stanična zbivanja. Postoji u dva oblika-reduciranom (GSH) koji može oksidirati do disulfida (GSSG), a njihov omjer određuje redoks stanje stanice koje je bitan posrednik u više procesa. U ovom radu obrađuju se uloge GSH kao regulatora staničnog redoks statusa u kontroli transkripcijskih faktora i imunološkog odgovora te kao kofaktora u sintezi proupalnih posrednika ili spoja s NO. Smanjenje razine GSH u uvjetima oksidacijskog stresa aktivira transkripcijske faktore NF-κB i AP-1 koji potiču ekspresiju mnogih proupalnih gena i gena za citokine. U imunološkom sustavu GSH ima dvojaku ulogu: utječe na smanjenje sinteze citokina koji mogu dodatno pojačati oksidacijski stres, a dovoljna količina GSH potrebna je za proliferaciju limfocita T i odgovarajući imunološki odgovor. GSH služi i kao kofaktor u pojedinim koracima sinteze proupalnih posrednika, leukotriena i prostaglandina, koje kataliziraju membranski enzimi porodice GSH S-transferaza imena MAPEG. NO se može spojiti s GSH pri čemu nastaje S-nitrozoglutation (GSNO) koji može posttranslacijskom modifikacijom preko S-tiolacije ili S-glutationilacije utjecati na aktivnost proteina i time inhibirati apoptozu ili utjecati na redoks stanje stanice.Glutathione (γ-glutamylcysteinylglycine, GSH) is a tripeptid present in large levels in all mammalian tissues. It is synthetized within the cells of all organs, especially in the liver. The largest levels of GSH are present in cytosol, mitochondria and ER. GSH serves as antioxidant, detoxifying agent in a number of metabolism processes and it modulates cell events. There are two forms of GSH: reduced form (GSH) which can oxidize to disulphide (GSSG), GSH/GSSG ratio determines redox state of cells which is important factor in many processes. This review explaines roles of GSH as a regulator of cellular processes in a modulation of transcriptional factors and immune responses and, also, as a cofactor in proinflammatory mediators synthesis and NO-adduct formation. In conditions of oxidative stress, a decrease in GSH levels activates transcriptional factors NF-κB i AP-1 which then activate pro-inflammatory genes and cytokine genes expression. GSH has a double role in the immune system: it affects the decrease in cytokine synthesis which can enhance oxidative stress and, also, adequate levels of GSH are essential for T lymphocyte proliferation and successful immune response. In the synthesis of pro-inflammatory mediators, leukotrienes and prostaglandins, GSH serves as a cofactor in some of the steps catalyzed by special GSH-S transferase membrane-bound enzymes called MAPEG. NO can form an adduct with GSH forming S-nitrosoglutathione (GSNO) which by posttranslational modification through Sthiolation and S-glutathionilation can modify protein activity and additionally apoptosis inhibition or cell redox state

Zanos i zablude Zagrebačkog salona arhitekture i urbanizma

Recenzija, prikaz 47. zagrebačkog salona – arhitektura i urbanizam 2009. – 2012., Gliptoteka, Zagreb, 29. studenog – 16. prosinca 2012

Influence of crystal defects on phase excitations in charge density waves

U ovoj disertaciji izučavan je utjecaj defekata na prijelaz u stanje vala gustoće naboja (VGN) i svojstva niskoenergetskih pobuđenja faze VGN-a, u ozračenim i dopiranim uzorcima VGN sistema o-TaS3. Smrzavanje fazne dinamike na temperaturi TG, kao dio složenih svojstva niskoenergetskih pobuđenja u VGN sistemima, posljedica je vezanja VGN-a sa defektima i slobodnim nosiocima naboja. Predloženi kriterij smrzavanja1, prema kojem je TG određena brojem slobodnih nosilaca naboja u domeni korelacije faze VGN-a je, kao glavni motiv istraživanja, u ovoj disertaciji potvrđen na uzorcima sa širokim rasponom udjela defekata. Transportna i dielektrična mjerenja, u širokom temperaturnom, naponskom i frekventnom području, pokazuju da defekti uzrokuju promjenu polja praga, niskofrekventne dinamike i dielektrične konstante, ali ne i linearne vodljivosti iznad TG, dok je ispod TG opažena samo promjena u linearnoj vodljivosti. Pokazano je da je zapinjanje faze u ozračenim uzorcima iznad TG jakog, a u dopiranim slabog karaktera. Ispod TG javlja se nelinearni kanal vodljivosti skokova varijabilnog dosega.In this dissertation the influence of defects on the transition to charge density wave (CDW) state and properties of low energy CDW phase excitations has been studied in irradiated and doped samples of CDW system o-TaS3. Phase dynamics freezing at a temperature TG, as a part of complex properties of low energy excitations in CDW systems, is a consequence of CDW coupling to defects and free charge carriers. As the main motive of this research, proposed freezing criterion1 (according to which TG is determined by a number of free charge carriers within a CDW phase correlation domain) has been confirmed in samples with a wide range of defects. Transport and dielectric measurements, over a wide temperature, voltage and frequency range, show that the defects influence the threshold field, low-frequency dynamics and dielectric constant, but not the linear conductivity above TG, while below TG only an influence on the linear conductivity has been observed. Strong and weak phase pinning mechanisms above TG are confirmed in irradiated and doped samples, respectively. Below TG variable range hopping type of nonlinear conductivity channel appears

Down Syndrome

Downov sindrom je najčešći genetski poremećaj koji nastaje uslijed viška jednog kromosoma. Broj kromosoma kod osobe urednog razvoja iznosi 46, a kod osoba s DS taj broj iznosi 47 kromosoma. Jedno od 650 novorođene djece rađa se s Downovim sindromom i bez obzira na rasu, vjeru, dob svatko može dobiti dijete s Downovim sindromom. U Republici Hrvatskoj se podaci o osobama s Downovim sindromom koja su ostvarila određena invalidska prava, prate u Registru osoba s invaliditetom. U navedenom Registru su prema stanju na dan 28. veljače 2017. g. registrirani parametri za 1607 osoba, s podjednakom distribucijom kod oba spola (835 muški; 772 ženske osobe s Downovim sindromom). Karakteristike izgleda djece s Downovim sindromom: rastu sporije nego djeca urednog razvoja, kosa je tanka, ravna, mekana, kod očiju karakterističan je kosi i uzak očni rasporak, lice je plosnato, nos je plosnat, usta trokutasta oblika, uške su male i obično niže smještene, vrat je kratak i širok. Veliki broj djece s Downovim sindromom imaju srčane mane, probleme s probavnim sustavom, poteškoće u funkcioniranju štitne žlijezde, te ozbiljne probleme vezane uz uho, grlo, nos. Intelektualne teškoće primarne su kod djece s Downovim sindromom i dijele se na četiri razine: laka intelektualna onesposobljenost, umjerena intelektualna onesposobljenost, teža intelektualna onesposobljenost, teška intelektualna onesposobljenost. Djeci s Downovim sindromom ne smije se oduzimati pravo na život u obitelji i smještati ih u institucije. Razvoj i promjene u društvu, složenost razvojnih faza djeteta doveli su i do promjene društvene svijesti o obitelji i njezinom utjecaju na cjelokupan razvoj djeteta. Jedna od osnovnih potreba djeteta je potreba za sigurnošću i razvojem stabilne veze s roditeljem. Od obitelji se očekuje poticanje i vođenje kroz djetetov razvoj u svoj njegovoj složenosti – kognitivni, fizički, socijalni, emocionalni, moralni, seksualni, duhovni, kulturni i obrazovni. Upravo ta višedimenzionalnost, obitelj odnosno roditeljstvo čini složenim.Down syndrome is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. The number of chromosomes in a person with a regular development is 46, and in a person with DS this number is 47 chromosomes. One of the 650 newborn babies is born with Down syndrome and regardless of race, religion, age anyone can get a child with Down syndrome. In the Republic of Croatia, data on persons with Down syndrome who have been assigned with certain disability rights are monitored in the Register of Persons with Disabilities. In a mentioned Register, on February 28, 2017, registered parameters for 1607 persons, with equal distribution in both sexes (835 males, 772 women with Down syndrome). Characteristics of the appearance of children with Down syndrome: Slightly slower than children with regular development, hair is thin, flat, soft, with eyes characteristic of hair and narrow eyelids, face is flat, nose is flat, mouth is triangular, small and usually lower positioned, neck short and wide. A large number of children with Down syndrome have heart defects, problems with the digestive system, difficulty in functioning of the thyroid gland, and serious problems with the ear, throat, nose. Intellectual disabilities are primary in children with Down syndrome and are divided into four levels: mild intellectual disability, moderate intellectual disability, severe intellectual disability and profound intellectual disability. Children with Down Syndrome should not be deprived of the right to family life and be placed in institutions. Development and change in society, the complexity of the child's developmental phases, have also led to a change in social awareness of the family and its impact on the overall development of the child. One of the basic needs of a child is the need for security and the development of a stable relationship with a parent. The family is expected to be guided through child development in its complexity - cognitive, physical, social, emotional, moral, sexual, spiritual, cultural and educational. It is this multi-dimensionality that makes the family or parenting complex