The treatment of human promyelocytic leukemia cell lines HL-60, and to some extent NB-4, with 1alpha,25-dihydroxyvitamin D(3) (VD3) induces differentiation toward the monocytic/macrophage lineage, demonstrated by the increased expression of CD11b and CD14, and the production of opsonized zymosan particles (OZP)-stimulated reactive oxygen species (ROS). Moreover, in more sensitive HL-60 cells, increased expression of 5-lipoxygenase (5-LPO), Mcl-1, IkappaB, and c-Jun, accompanied by the activation of p38 MAPK, was detected. These VD3 effects on HL-60 cell differentiation were significantly potentiated by 5-LPO inhibitors MK-886 and AA-861 and were inverted by SB202190 (SB), a p38 MAPK inhibitor. The inhibition of differentiation by SB was demonstrated by a reduction of CD14 expression and by a decrease in OZP-activated ROS production. These results indicated that p38 MAPK pathway is involved in 5-LPO inhibitors-dependent potentiation of VD3-induced monocytic differentiation.

• MeSH
• arachidonát-5-lipoxygenasa genetika   MeSH
• benzochinony farmakologie   MeSH
• buněčná diferenciace účinky léků   MeSH
• HL-60 buňky MeSH
• indoly farmakologie   MeSH
• inhibitory lipoxygenas farmakologie   MeSH
• lidé MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• monocyty cytologie   MeSH
• vitamin D analogy a deriváty   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone MeSH Prohlížeč
• arachidonát-5-lipoxygenasa MeSH
• benzochinony MeSH
• dihydroxy-vitamin D3 MeSH Prohlížeč
• indoly MeSH
• inhibitory lipoxygenas MeSH
• mitogenem aktivované proteinkinasy p38 MeSH
• MK-886 MeSH Prohlížeč
• vitamin D MeSH

This article comments on: Vladimir Y. Gorshkov, Yana Y. Toporkova, Ivan D. Tsers, Elena O. Smirnova, Anna V. Ogorodnikova, Natalia E. Gogoleva, Olga I. Parfirova, Olga E. Petrova, and Yuri V. Gogolev, Differential modulation of the lipoxygenase cascade during typical and latent Pectobacterium atrosepticum infections, Annals of Botany, Volume 129, Issue 3, 16 Februray 2022, Pages 271–285 https://doi.org/10.1093/aob/mcab108

• Klíčová slova
• Lipoxygenase pathway, Pectobacterium atrosepticum, typical and latent infections,
• MeSH
• lipoxygenasa MeSH
• nemoci rostlin mikrobiologie   MeSH
• oxylipiny * MeSH
• Pectobacterium * MeSH
• Publikační typ
• komentáře MeSH
• práce podpořená grantem MeSH
• úvodníky MeSH
• Názvy látek
• lipoxygenasa MeSH
• oxylipiny * MeSH

Inhibitors of arachidonic acid (AA) conversion were described as suppressors of proliferation and inducers of differentiation of various leukemic cells. Certain AA metabolites have been shown to cooperate with Jun proteins that are important factors controlling cell proliferation, differentiation and apoptosis. Using lipoxygenase (LOX) inhibitors of various specifity we studied possible participation of lipoxygenase pathway in regulation of proliferation and apoptosis of v-myb-transformed chicken monoblasts BM2 and its functional interaction with Jun proteins. We found that nordihydroguaiaretic acid (NDGA) and esculetin (Esc) negatively regulate proliferation of BM2 cells causing accumulation in either G0/G1-phase (nordihydroguaiaretic acid) or S-phase (esculetin) of the cell cycle. BM2 cells can be also induced to undergo growth arrest and partial differentiation by ectopic expression of Jun proteins. We demonstrated that lipoxygenase inhibitors further enforce tumor suppressive capabilities of Jun proteins by inducing either more efficient cell cycle block and/or apoptosis in BM2 cells. This suggests that there is a cross-talk between the lipoxygenase- and Jun-directed pathways in regulation of differentiation and proliferation of monoblastic cells. Thus pharmacologic agents that specifically block lipoxygenase-catalyzed activity and enforce the effects of differentiation-inducers may be important components in anti-tumor therapies.

• MeSH
• antioxidancia farmakologie   MeSH
• apoptóza MeSH
• buněčné dělení účinky léků   MeSH
• buněčný cyklus účinky léků   MeSH
• geny myb * MeSH
• inhibitory lipoxygenas farmakologie   MeSH
• kultivované buňky MeSH
• kur domácí MeSH
• kyselina 5,8,11,14-eikosatetraenová metabolismus   MeSH
• kyselina nordihydroguaiaretová farmakologie   MeSH
• kyseliny arachidonové metabolismus   MeSH
• lidé MeSH
• lipoxygenasa metabolismus   MeSH
• monocyty cytologie   účinky léků   fyziologie   MeSH
• protoonkogenní proteiny c-jun genetika   metabolismus   MeSH
• umbeliferony farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antioxidancia MeSH
• esculetin MeSH Prohlížeč
• inhibitory lipoxygenas MeSH
• kyselina 5,8,11,14-eikosatetraenová MeSH
• kyselina nordihydroguaiaretová MeSH
• kyseliny arachidonové MeSH
• lipoxygenasa MeSH
• protoonkogenní proteiny c-jun MeSH
• umbeliferony MeSH

A new heteroleptic copper(II) compound named C0-UDCA was prepared by reaction of [Cu(phen)2(OH2)](ClO4)2 (C0) with the bile ursodeoxycholic acid (UDCA). The resulting compound is able to inhibit the lipoxygenase enzyme showing more efficacy than the precursors C0 and UDCA. Molecular docking simulations clarified the interactions with the enzyme as due to allosteric modulation. The new complex shows antitumoral effect on ovarian (SKOV-3) and pancreatic (PANC-1) cancer cells at the Endoplasmic Reticulum (ER) level by activating the Unfolded Protein Response. In particular, the chaperone BiP, the pro-apoptotic protein CHOP and the transcription factor ATF6 are upregulated in the presence of C0-UDCA. The combination of Intact Cell MALDI-MS and statistical analysis have allowed us to discriminate between untreated and treated cells based on their mass spectrometry fingerprints.

• Klíčová slova
• Copper complex, ER stress, Lipoxygenase, Mass spectrometry, Molecular docking, Solution equilibria,
• MeSH
• apoptóza MeSH
• buněčné linie MeSH
• fenantroliny chemie   MeSH
• inhibitory enzymů farmakologie   MeSH
• inhibitory lipoxygenas * farmakologie   MeSH
• kyselina ursodeoxycholová farmakologie   MeSH
• měď farmakologie   chemie   MeSH
• nádory slinivky břišní MeSH
• nádory * MeSH
• simulace molekulového dockingu MeSH
• stres endoplazmatického retikula MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fenantroliny MeSH
• inhibitory enzymů MeSH
• inhibitory lipoxygenas * MeSH
• kyselina ursodeoxycholová MeSH
• měď MeSH

The effects of inhibitors of arachidonic acid oxidative metabolism, gamma-radiation and/or their combinations on proliferation and cell cycle were studied in human breast carcinoma HS578T and monoblastoid U937 cell lines. While piroxicam an inhibitor of cyclooxygenase pathway, had no significant effects on cell proliferation, inhibitors of lipoxygenase pathway, nordihydroguaiaretic acid and esculetin, suppressed [3H]-thymidine incorporation and cell growth. The latter agents also differed in their modulation of cell cycle parameters depending on the cell line and the time of treatment. When the cells were preirradiated with gamma radiation (5 Gy) and treated with the drugs (at concentrations 50 mumol/l and higher) the effects on cell proliferation were mostly additive. On the other hand, the results suggest that antiproliferative effects could be significantly strengthened when lower doses (25 mumol/l) of lipoxygenase inhibitors were combined with a low dose (1 Gy) of gamma-radiation. Experiments monitoring the reversibility of the effects after single or combined treatment with the agents showed that irradiation suppressed the ability of U937 cells to restore cell proliferation, and that these effects may be strenghtened by esculetin. In conclusion, our results (1) suggest that the lipoxygenase pathway plays a significant role in proliferation of cancer HS578T and U937 cells in vitro, and (2) implicate the possibility of more effective antiproliferative effects after combined treatment of cells with gamma-radiation and lipoxygenase inhibitors.

• MeSH
• buněčné dělení účinky léků   účinky záření   MeSH
• buněčné linie MeSH
• buněčný cyklus účinky léků   účinky záření   MeSH
• DNA nádorová biosyntéza   MeSH
• inhibitory cyklooxygenasy farmakologie   MeSH
• inhibitory lipoxygenas farmakologie   MeSH
• kinetika MeSH
• kyselina nordihydroguaiaretová farmakologie   MeSH
• lidé MeSH
• nádorové buňky kultivované MeSH
• nádory prsu MeSH
• piroxikam farmakologie   MeSH
• thymidin metabolismus   MeSH
• umbeliferony farmakologie   MeSH
• viabilita buněk účinky léků   účinky záření   MeSH
• vztah dávky záření a odpovědi MeSH
• záření gama MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA nádorová MeSH
• esculetin MeSH Prohlížeč
• inhibitory cyklooxygenasy MeSH
• inhibitory lipoxygenas MeSH
• kyselina nordihydroguaiaretová MeSH
• piroxikam MeSH
• thymidin MeSH
• umbeliferony 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
• Názvy látek
• lipoxygenasa MeSH
• lipoxygenase 2, Arabidopsis MeSH Prohlížeč
• lipoxygenasy MeSH
• mastné kyseliny MeSH
• proteiny huseníčku MeSH
• singletový kyslík MeSH

Inhibitors of the lipoxygenase pathway of arachidonic acid metabolism represent a potential anti-tumor drugs. These compounds have been found to inhibit the growth and induce the apoptosis of various tumor cells both in vitro and in vivo. In this study, the effects of the lipoxygenase inhibitors esculetin and nordihydroguaiaretic acid (NDGA) on the progression of the cell cycle were investigated in eight mammalian cell lines of different origin. Flow cytometric analyses of cell cycle distribution after staining of DNA with propidium iodide or 7-aminoactinomycin D and DNA synthesis using incorporation of 5-bromo-2'-deoxy-uridine showed that both esculetin and NDGA suppress cell growth by interrupting the progression of cells through S-phase that results in their accumulation in this phase of the cell cycle. The possible mechanisms of these effects and the significance of the findings for the improvement of anticancer therapy targeted on cell cycle is discussed.

• MeSH
• antioxidancia farmakologie   MeSH
• bromodeoxyuridin MeSH
• buněčné dělení účinky léků   MeSH
• DNA nádorová metabolismus   MeSH
• inhibitory lipoxygenas farmakologie   MeSH
• kyselina arachidonová metabolismus   MeSH
• kyselina nordihydroguaiaretová farmakologie   MeSH
• lidé MeSH
• myši MeSH
• nádorové buňky kultivované účinky léků   patologie   MeSH
• propidium metabolismus   MeSH
• replikace DNA MeSH
• S fáze účinky léků   genetika   MeSH
• techniky in vitro MeSH
• umbeliferony farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antioxidancia MeSH
• bromodeoxyuridin MeSH
• DNA nádorová MeSH
• esculetin MeSH Prohlížeč
• inhibitory lipoxygenas MeSH
• kyselina arachidonová MeSH
• kyselina nordihydroguaiaretová MeSH
• propidium MeSH
• umbeliferony MeSH

Leukotrienes (LTs) and sphingolipids are critical lipid mediators participating in numerous cellular signal transduction events and developing various disorders, such as bronchial hyperactivity leading to asthma. Enzymatic reactions initiating production of these lipid mediators involve 5-lipoxygenase (5-LO)-mediated conversion of arachidonic acid to LTs and serine palmitoyltransferase (SPT)-mediated de novo synthesis of sphingolipids. Previous studies have shown that endoplasmic reticulum membrane protein ORM1-like protein 3 (ORMDL3) inhibits the activity of SPT and subsequent sphingolipid synthesis. However, the role of ORMDL3 in the synthesis of LTs is not known. In this study, we used peritoneal-derived mast cells isolated from ORMDL3 KO or control mice and examined their calcium mobilization, degranulation, NF-κB inhibitor-α phosphorylation, and TNF-α production. We found that peritoneal-derived mast cells with ORMDL3 KO exhibited increased responsiveness to antigen. Detailed lipid analysis showed that compared with WT cells, ORMDL3-deficient cells exhibited not only enhanced production of sphingolipids but also of LT signaling mediators LTB4, 6t-LTB4, LTC4, LTB5, and 6t-LTB5. The crosstalk between ORMDL3 and 5-LO metabolic pathways was supported by the finding that endogenous ORMDL3 and 5-LO are localized in similar endoplasmic reticulum domains in human mast cells and that ORMDL3 physically interacts with 5-LO. Further experiments showed that 5-LO also interacts with the long-chain 1 and long-chain 2 subunits of SPT. In agreement with these findings, 5-LO knockdown increased ceramide levels, and silencing of SPTLC1 decreased arachidonic acid metabolism to LTs to levels observed upon 5-LO knockdown. These results demonstrate functional crosstalk between the LT and sphingolipid metabolic pathways, leading to the production of lipid signaling mediators.

• Klíčová slova
• ER membrane domains, HPLC, immunology, inflammation, leukotrienes, lipid mass spectrometry, peritoneal-derived mast cells, signal transduction, sphingolipids,
• MeSH
• arachidonát-5-lipoxygenasa metabolismus   MeSH
• ikosanoidy analýza   metabolismus   MeSH
• membránové proteiny metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• serin-C-palmitoyltransferasa metabolismus   MeSH
• sfingolipidy analýza   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• arachidonát-5-lipoxygenasa MeSH
• ikosanoidy MeSH
• membránové proteiny MeSH
• ORMDL3 protein, mouse MeSH Prohlížeč
• serin-C-palmitoyltransferasa MeSH
• sfingolipidy MeSH

Stilbenoids are important components of foods (e.g., peanuts, grapes, various edible berries), beverages (wine, white tea), and medicinal plants. Many publications have described the anti-inflammatory potential of stilbenoids, including the widely known trans-resveratrol and its analogues. However, comparatively little information is available regarding the activity of their prenylated derivatives. One new prenylated stilbenoid (2) was isolated from Artocarpus altilis and characterized structurally based on 1D and 2D NMR analysis and HRMS. Three other prenylated stilbenoids were prepared synthetically (9-11). Their antiphlogistic potential was determined by testing them together with known natural prenylated stilbenoids from Macaranga siamensis and Artocarpus heterophyllus in both cell-free and cell assays. The inhibition of 5-lipoxygenase (5-LOX) was also shown by simulated molecular docking for the most active stilbenoids in order to elucidate the mode of interaction between these compounds and the enzyme. Their effects on the pro-inflammatory nuclear factor-κB (NF-κB) and the activator protein 1 (AP-1) signaling pathway were also analyzed. The THP1-XBlue-MD2-CD14 cell line was used as a model for determining their anti-inflammatory potential, and lipopolysaccharide (LPS) stimulation of Toll-like receptor 4 induced a signaling cascade leading to the activation of NF-κB/AP-1. The ability of prenylated stilbenoids to attenuate the production of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) was further evaluated using LPS-stimulated THP-1 macrophages.

• MeSH
• buněčné linie MeSH
• cyklooxygenasy metabolismus   MeSH
• inhibitory enzymů farmakologie   MeSH
• lidé MeSH
• lipoxygenasy metabolismus   MeSH
• NF-kappa B antagonisté a inhibitory   MeSH
• prenylace * MeSH
• signální transdukce účinky léků   MeSH
• stilbeny farmakologie   MeSH
• transkripční faktor AP-1 antagonisté a inhibitory   MeSH
• zánět prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cyklooxygenasy MeSH
• inhibitory enzymů MeSH
• lipoxygenasy MeSH
• NF-kappa B MeSH
• stilbeny MeSH
• transkripční faktor AP-1 MeSH

Cyclooxygenases and lipoxygenases are proinflammatory enzymes; the former affects platelet aggregation, vasoconstriction, vasodilatation and later the development of atherosclerosis. Red wines from Georgia and central and western Europe inhibited cyclooxygenase-1 (COX-1) activity in the range of 63-94%, cyclooxygenase-2 (COX-2) activity in the range of 20-44% (tested at a concentration of 5 mL/L), and 5-lipoxygenase (5-LOX) activity in the range of 72-84% (at a concentration of 18.87 mL/L). White wines inhibited 5-LOX in the range of 41-68% at a concentration of 18.87 mL/L and did not inhibit COX-1 and COX-2. Piceatannol (IC50 = 0.76 μM) was identified as a strong inhibitor of 5-LOX followed by luteolin (IC50 = 2.25 μM), quercetin (IC50 = 3.29 μM), and myricetin (IC50 = 4.02 μM). trans-Resveratrol was identified as an inhibitor of COX-1 (IC50 = 2.27 μM) and COX-2 (IC50 = 3.40 μM). Red wine as a complex mixture is a powerful inhibitor of COX-1, COX-2, and 5-LOX, the enzymes involved in eicosanoid biosynthetic pathway.

• MeSH
• aktivace enzymů účinky léků   MeSH
• arachidonát-5-lipoxygenasa metabolismus   MeSH
• cyklooxygenasa 1 metabolismus   MeSH
• cyklooxygenasa 2 metabolismus   MeSH
• flavonoidy farmakologie   MeSH
• inhibitory cyklooxygenasy farmakologie   MeSH
• katalýza MeSH
• lidé MeSH
• quercetin farmakologie   MeSH
• resveratrol MeSH
• stilbeny farmakologie   MeSH
• víno * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• arachidonát-5-lipoxygenasa MeSH
• cyklooxygenasa 1 MeSH
• cyklooxygenasa 2 MeSH
• flavonoidy MeSH
• inhibitory cyklooxygenasy MeSH
• myricetin MeSH Prohlížeč
• quercetin MeSH
• resveratrol MeSH
• stilbeny MeSH