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
Plant oxylipins form a constantly growing group of signaling molecules that comprise oxygenated fatty acids and metabolites derived therefrom. In the last decade, the understanding of biosynthesis, metabolism, and action of oxylipins, especially jasmonates, has dramatically improved. Additional mechanistic insights into the action of enzymes and insights into signaling pathways have been deepened for jasmonates. For other oxylipins, such as the hydroxy fatty acids, individual signaling properties and cross talk between different oxylipins or even with additional phytohormones have recently been described. This review summarizes recent understanding of the biosynthesis, regulation, and function of oxylipins.
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
In the current study, singlet oxygen formation by lipid peroxidation induced by heat stress (40 °C) was studied in vivo in unicellular green alga Chlamydomonas reinhardtii. Primary and secondary oxidation products of lipid peroxidation, hydroperoxide and malondialdehyde, were generated under heat stress as detected using swallow-tailed perylene derivative fluorescence monitored by confocal laser scanning microscopy and high performance liquid chromatography, respectively. Lipid peroxidation was initiated by enzymatic reaction as inhibition of lipoxygenase by catechol and caffeic acid prevented hydroperoxide formation. Ultra-weak photon emission showed formation of electronically excited species such as triplet excited carbonyl, which, upon transfer of excitation energy, leads to the formation of either singlet excited chlorophyll or singlet oxygen. Alternatively, singlet oxygen is formed by direct decomposition of hydroperoxide via Russell mechanisms. Formation of singlet oxygen was evidenced by the nitroxyl radical 2,2,6,6-tetramethylpiperidine-1-oxyl detected by electron paramagnetic resonance spin-trapping spectroscopy and the imaging of green fluorescence of singlet oxygen sensor green detected by confocal laser scanning microscopy. Suppression of singlet oxygen formation by lipoxygenase inhibitors indicates that singlet oxygen may be formed via enzymatic lipid peroxidation initiated by lipoxygenase.
- MeSH
- Chlamydomonas reinhardtii metabolismus MeSH
- lipoxygenasa metabolismus MeSH
- malondialdehyd metabolismus MeSH
- peroxidace lipidů fyziologie MeSH
- reakce na tepelný šok fyziologie MeSH
- rostlinné proteiny metabolismus MeSH
- singletový kyslík metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Coumarins represent a large group of 1,2-benzopyrone derivatives which have been identified in many natural sources and synthetized as well. Several studies have shown that their antioxidant capacity is not based only on direct scavenging of reactive oxygen and nitrogen species (RONS) but other mechanisms are also involved. These include: a) the chelation of transient metals iron and copper, which are known to catalyse the Fenton reaction; and b) the inhibition of RONS-producing enzymes (e.g. xanthine oxidase, myeloperoxidase and lipoxygenase), suggesting that mechanism(s) involved on cellular level are complex and synergistic. Moreover, many factors must be taken into account when analysing structure-antioxidant capacity relationships of coumarins due to different in vitro/in vivo methodological approaches. The structural features necessary for the direct RONS scavenging and metal chelation are apparently similar and the ideal structures are 6,7-dihydroxy- or 7,8-dihydroxycoumarins. However, the clinical outcome is unknown, because these coumarins are able to reduce copper and iron, and may thus paradoxically potentiate the Fenton chemistry. The similar structural features appear to be associated with inhibition of lipoxygenase, probably due to interference with iron in its active site. Contrarily, 6,7-dihydroxycoumarin seems to be the most active coumarin in the inhibition of xanthine oxidase while its derivative bearing the 4-methyl group or 7,8-dihydroxycoumarin are less active or inactive. In addition, coumarins may hinder the induction of inducible NO-synthase and cyclooxygenase- 2. Sparse data on inhibition of myeloperoxidase do not enable any clear conclusion, but some coumarins may block it.
- MeSH
- chelátory chemie metabolismus farmakologie MeSH
- cyklooxygenasa 2 metabolismus MeSH
- inhibitory enzymů chemie metabolismus farmakologie MeSH
- kumariny chemie metabolismus farmakologie MeSH
- lidé MeSH
- lipoxygenasa metabolismus MeSH
- měď chemie metabolismus MeSH
- oxidační stres účinky léků MeSH
- peroxidasa antagonisté a inhibitory metabolismus MeSH
- reaktivní formy kyslíku antagonisté a inhibitory metabolismus MeSH
- scavengery volných radikálů chemie metabolismus farmakologie MeSH
- synthasa oxidu dusnatého, typ II antagonisté a inhibitory metabolismus MeSH
- vztahy mezi strukturou a aktivitou MeSH
- xanthinoxidasa antagonisté a inhibitory metabolismus MeSH
- železo chemie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Reactive oxygen species formed as a response to various abiotic and biotic stresses cause an oxidative damage of cellular component such are lipids, proteins and nucleic acids. Lipid peroxidation is considered as one of the major processes responsible for the oxidative damage of the polyunsaturated fatty acid in the cell membranes. Various methods such as a loss of polyunsaturated fatty acids, amount of the primary and the secondary products are used to monitor the level of lipid peroxidation. To investigate the use of ultra-weak photon emission as a non-invasive tool for monitoring of lipid peroxidation, the involvement of lipid peroxidation in ultra-weak photon emission was studied in the unicellular green alga Chlamydomonas reinhardtii. Lipid peroxidation initiated by addition of exogenous linoleic acid to the cells was monitored by ultra-weak photon emission measured with the employment of highly sensitive charged couple device camera and photomultiplier tube. It was found that the addition of linoleic acid to the cells significantly increased the ultra-weak photon emission that correlates with the accumulation of lipid peroxidation product as measured using thiobarbituric acid assay. Scavenging of hydroxyl radical by mannitol, inhibition of intrinsic lipoxygenase by catechol and removal of molecular oxygen considerably suppressed ultra-weak photon emission measured after the addition of linoleic acid. The photon emission dominated at the red region of the spectrum with emission maximum at 680 nm. These observations reveal that the oxidation of linoleic acid by hydroxyl radical and intrinsic lipoxygenase results in the ultra-weak photon emission. Electronically excited species such as excited triplet carbonyls are the likely candidates for the primary excited species formed during the lipid peroxidation, whereas chlorophylls are the final emitters of photons. We propose here that the ultra-weak photon emission can be used as a non-invasive tool for the detection of lipid peroxidation in the cell membranes.
- MeSH
- buněčná membrána účinky léků metabolismus MeSH
- Chlamydomonas reinhardtii cytologie účinky léků metabolismus MeSH
- fotony MeSH
- histidin farmakologie MeSH
- hydroxylový radikál metabolismus MeSH
- inhibitory lipoxygenas farmakologie MeSH
- kyselina linolová farmakologie MeSH
- kyslík metabolismus MeSH
- lipoxygenasa metabolismus MeSH
- malondialdehyd metabolismus MeSH
- mannitol farmakologie MeSH
- peroxidace lipidů účinky léků MeSH
- thiobarbituráty metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Lipoxygenases (LOX; linoleate:oxygen oxidoreductase, EC 1.13.11.12) are a family of dioxygenases that do not contain hem-bonded iron at the active site. They catalyze peroxidation of polyunsaturated fatty acids, in particular linolic and linolenic acids, which gives hydroperoxy derivatives of (9S)- or (13S)-polyunsaturated fatty acids (9-LOX or 13-LOX, respectively). Lipid peroxidation is important in plant evolution and for their response to various forms of stress, both of biotic and abiotic origin. LOX is the starting enzyme of the lipoxygenase metabolic pathway producing oxylipins such as signal molecules, antimicrobial and antifungal compounds.
Natural polyphenols are a wide class of secondary plant metabolites and represent an abundant antioxidant component of human diet. An important, but often neglected group of natural polyphenols, are tannins. This review offers a general description of chemistry of both hydrolysable and condensed tannins (proanthocyanidins), the mechanisms of their antioxidation action, like free radical scavenging activity, chelation of transition metals, inhibition of prooxidative enzymes and lipid peroxidation. The mechanisms of action of antibacterial, antiviral, anticarcinogenic, cardiovascular system preventing, and antiinflammatory effects as well as the absorption, metabolic fate and positive in vivo effects of tannins are enclosed.
- MeSH
- antiflogistika nesteroidní farmakologie chemie terapeutické užití MeSH
- antiinfekční látky farmakologie chemie terapeutické užití MeSH
- antikarcinogenní látky farmakologie chemie terapeutické užití MeSH
- antioxidancia farmakologie chemie terapeutické užití MeSH
- financování organizované MeSH
- hydrolyzovatelné taniny farmakologie chemie terapeutické užití MeSH
- křenová peroxidasa antagonisté a inhibitory MeSH
- lidé MeSH
- lipoxygenasa účinky léků MeSH
- peroxidace lipidů účinky léků MeSH
- synthasa oxidu dusnatého antagonisté a inhibitory MeSH
- zdraví MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
