Leukotriény sú silné mediátory zápalových procesov v organizme. Možnosti inhibície ich biosyntézy bolí intenzívne študované s cielom vyvinút nové spósoby terapie zápalových ochorení, zvlášt astmy. Biosyntéza všetkých leukotriénov je závislá na tvorbe klúčového medziproduktu LTA4, Enzým 5-lipoxygenáza v súčinnosti s FLAP, katalyzuje premenu kyseliny arachidonovej na LTA4, V práci sa diskutuje súčasný vývoj nových liečiv v tejto oblasti terapie.

Leukotrienes are powerfizl mediators of inflammation processes. Possibilities of their biosynthesis inhibition have been intensively studied during recent two decades aiming to develop new methods of therapy of various inflammatory diseases, particularly asthma. Biosynthesis of all leukotrienes is dependent on the production of the key intermediate LTA4, Transformation of arachidonic acid to LTA4 is catalyzed by the enzyme 5-lipoxygenase and faciliated by FLAP. The present paper discusses the results of recent development of new drugs in this area.

• MeSH
• antagonisté leukotrienů MeSH
• antioxidancia chemie   MeSH
• farmakoterapie metody   MeSH
• inhibitory lipoxygenas chemie   MeSH
• leukotrieny biosyntéza   MeSH
• zánět farmakoterapie   MeSH

• MeSH
• anthraceny MeSH
• inhibitory lipoxygenas MeSH
• izoenzymy MeSH
• lipoxygenasa MeSH
• Publikační typ
• vysokoškolské kvalifikační práce MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• biochemie

Recent research has highlighted the pivotal role of lipoxygenases in modulating ferroptosis and immune responses by catalyzing the generation of lipid peroxides. However, the limitations associated with protein enzymes, such as poor stability, low bioavailability, and high production costs, have motivated researchers to explore biomimetic materials with lipoxygenase-like activity. Here, we report the discovery of lipoxygenase-like two-dimensional (2D) MoS2nanosheets capable of catalyzing lipid peroxidation and inducing ferroptosis. The resulting catalytic products were successfully identified using mass spectrometry and a luminescent substrate. Unlike native lipoxygenases, MoS2 nanosheets exhibited exceptional catalytic activity at extreme pH, high temperature, high ionic strength, and organic solvent conditions. Structure-activity relationship analysis indicates that sulfur atomic vacancy sites on MoS2 nanosheets are responsible for their catalytic activity. Furthermore, the lipoxygenase-like activity of MoS2 nanosheets was demonstrated within mammalian cells and animal tissues, inducing distinctive ferroptotic cell death. In summary, this research introduces an alternative to lipoxygenase to regulate lipid peroxidation in cells, offering a promising avenue for ferroptosis induction.

• MeSH
• biomimetické materiály chemie   farmakologie   metabolismus   MeSH
• disulfidy * chemie   metabolismus   MeSH
• ferroptóza * účinky léků   MeSH
• katalýza MeSH
• lidé MeSH
• lipoxygenasa * metabolismus   chemie   MeSH
• molybden chemie   metabolismus   MeSH
• myši MeSH
• nanostruktury chemie   MeSH
• peroxidace lipidů MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Geranyl flavones have been studied as compounds that potentially can be developed as anti-inflammatory agents. A series of natural geranylated flavanones was isolated from Paulownia tomentosa fruits, and these compounds were studied for their anti-inflammatory activity and possible mechanism of action. Two new compounds were characterized [paulownione C (17) and tomentodiplacone O (20)], and all of the isolated derivatives were assayed for their ability to inhibit cyclooxygenases (COX-1 and COX-2) and 5-lipoxygenase (5-LOX). The compounds tested showed variable degrees of activity, with several of them showing activity comparable to or greater than the standards used in COX-1, COX-2, and 5-LOX assays. However, only the compound tomentodiplacone O (20) showed more selectivity against COX-2 versus COX-1 when compared with ibuprofen. The ability of the test compounds to interact with the above-mentioned enzymes was supported by docking studies, which revealed the possible incorporation of selected test substances into the active sites of these enzymes. Furthermore, one of the COX/LOX dual inhibitors, diplacone (14) (a major geranylated flavanone of P. tomentosa), was studied in vitro to obtain a proteomic overview of its effect on inflammation in LPS-treated THP-1 macrophages, supporting its previously observed anti-inflammatory activity and revealing the mechanism of its anti-inflammatory effect.

• MeSH
• antiflogistika chemie   izolace a purifikace   farmakologie   MeSH
• arachidonát-5-lipoxygenasa metabolismus   MeSH
• cyklooxygenasa 1 metabolismus   MeSH
• cyklooxygenasa 2 metabolismus   MeSH
• flavonoidy chemie   izolace a purifikace   farmakologie   MeSH
• inhibitory cyklooxygenasy 2 chemie   izolace a purifikace   farmakologie   MeSH
• inhibitory lipoxygenas chemie   izolace a purifikace   farmakologie   MeSH
• Magnoliopsida chemie   MeSH
• molekulární struktura MeSH
• ovoce chemie   MeSH
• proteomika * MeSH
• Publikační typ
• časopisecké články MeSH

Wounding, one of the most intensive stresses influencing plants ontogeny and lifespan, can be induced by herbivory as well as by physical factors. Reactive oxygen species play indispensable role both in the local and systemic defense reactions which enable "reprogramming" of metabolic pathways to set new boundaries and physiological equilibrium suitable for survival. In our current study, we provide experimental evidence on the formation of singlet oxygen (1O2) after wounding of Arabidopsis leaves. It is shown that 1O2 is formed by triplet-triplet energy transfer from triplet carbonyls to molecular oxygen. Using lipoxygenase inhibitor catechol, it is demonstrated that lipid peroxidation is initiated by lipoxygenase. Suppression of 1O2 formation in lox2 mutant which lacks chloroplast lipoxygenase indicates that lipoxygenase localized in chloroplast is predominantly responsible for 1O2 formation. Interestingly, 1O2 formation is solely restricted to chloroplasts localized at the wounding site. Data presented in this study might provide novel insight into wound-induced signaling in the local defense reaction.

• MeSH
• Arabidopsis MeSH
• fenotyp MeSH
• fluorescenční protilátková technika MeSH
• konfokální mikroskopie MeSH
• lipoxygenasa metabolismus   MeSH
• lipoxygenasy genetika   MeSH
• mastné kyseliny metabolismus   MeSH
• molekulární zobrazování MeSH
• mutace MeSH
• proteiny huseníčku genetika   MeSH
• rány a poranění metabolismus   MeSH
• singletový kyslík metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• antioxidancia farmakologie   izolace a purifikace   MeSH
• dibenzyly farmakologie   izolace a purifikace   MeSH
• inhibitory lipoxygenas farmakologie   izolace a purifikace   MeSH
• isochinoliny farmakologie   izolace a purifikace   MeSH
• léčivé rostliny chemie   MeSH
• peroxidace lipidů MeSH
• rostlinné extrakty farmakologie   chemie   MeSH

• MeSH
• buněčné dělení účinky léků   MeSH
• finanční podpora výzkumu jako téma MeSH
• inhibitory lipoxygenas MeSH
• kultivované buňky MeSH
• kur domácí MeSH
• lidé MeSH
• lipoxygenasa metabolismus   MeSH
• monocyty účinky léků   MeSH
• protoonkogenní proteiny c-jun metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH

• MeSH
• antioxidancia farmakologie   MeSH
• finanční podpora výzkumu jako téma MeSH
• inhibitory lipoxygenas farmakologie   MeSH
• kyselina nordihydroguaiaretová farmakologie   MeSH
• lidé MeSH
• myši MeSH
• S fáze účinky záření   MeSH
• techniky in vitro MeSH
• umbeliferony farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH

Leukotrienes play an important role in the inflammatory process accompanying allergic diseases of respiratory, gastrointestinal and dermatological systems. Leukotrienes are generated from arachidonic acid as a result of the 5-lipoxygenase action. This paper deals with 5-lipoxygenase action mechanism and the following biosynthesis of all leukotrienes. In this article, potential antileukotrienic agents are classified according to their mechanism of action. The original antileukotrienic compounds of the Research Institute for Pharmacy and Biochemistry in Prague (VUFB), Czech Republic are presented in a separate chapter of the paper.

• MeSH
• antagonisté leukotrienů farmakologie   MeSH
• antiastmatika farmakologie   MeSH
• antiflogistika farmakologie   MeSH
• arachidonát-5-lipoxygenasa metabolismus   MeSH
• financování organizované MeSH
• inhibitory lipoxygenas MeSH
• kyseliny arachidonové metabolismus   MeSH
• leukotrieny biosyntéza   MeSH
• lidé MeSH
• substrátová specifita MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• kyseliny arachidonové metabolismus   MeSH
• lipoxygenasa metabolismus   MeSH
• Publikační typ
• sborníky MeSH

• Konspekt
• Fyziologie člověka a srovnávací fyziologie
• NLK Obory
• fyziologie
• biochemie