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Autor: Šimek, Vladimír

11 záznamů v Medvik Filtry

Článek

MK-886 enhances tumour necrosis factor-alpha-induced differentiation and apoptosis

Cancer letters. 2006 ; 237 (2) : 263-271.

ISSN 0304-3835
Medvik
Zdroj

We investigated the role of the 5-lipoxygenase (5-LOX) pathway of arachidonic acid metabolism in tumour necrosis factor-alpha (TNF-alpha)-induced differentiation of human leukemic HL-60 cells using MK-886, an inhibitor of 5-LOX activating protein. MK-886 augmented cell cycle arrest and differentiation induced by TNF-alpha; however, both effects were probably 5-LOX-independent, because a general LOX inhibitor, NDGA, had no effect. Apoptosis was significantly elevated after combined TNF-alpha and MK-886 treatment, which could be partially associated with changes of Mcl-1 protein expression. NF-kappaB signalling or activation of JNKs were not modulated by MK-886. Thus, in addition to apoptosis, MK-886 can enhance TNF-alpha-induced differentiation.

MeSH
apoptóza MeSH
arachidonát-5-lipoxygenasa metabolismus MeSH
buněčná diferenciace MeSH
buněčný cyklus MeSH
časové faktory MeSH
financování organizované MeSH
HL-60 buňky MeSH
indoly farmakologie MeSH
inhibitory lipoxygenas farmakologie MeSH
lidé MeSH
nádorové buněčné linie MeSH
signální transdukce MeSH
TNF-alfa metabolismus MeSH
viabilita buněk MeSH
Check Tag
lidé MeSH

Článek

Nitric oxide production by hemocytes of larva and pharate prepupa of Galleria mellonella in response to bacterial lipopolysaccharide: Cytoprotective or cytotoxic?

Comparative biochemistry and physiology. C. Toxicology & farmacology. 2006 ; 142 (1-2) : 103-110.

ISSN 1532-0456
Medvik
Zdroj

Nitric oxide production by the hemocytes of the last instar larvae and sessile pharate prepupa of Galleria mellonella (Lepidoptera: Pyralidae) was demonstrated in vitro in response to preparations of bacterial lipopolysaccharide (LPS) from Escherichia coli using the Griess reaction. Augmented, dose dependent nitric oxide production was observed in the pharate prepupal hemocytes compared with larval hemocytes. This was partially reversed in a dose dependent manner with S-methyl thiourea (SMT), a specific inhibitor of inducible nitric oxide synthase (iNOS). A decrease in NO production was also observed when non-selective inhibitors such as N(G)-nitro-L-arginine (L-NAME) and N-omega-nitro-L-arginine (L-NNA) were used, albeit the inhibition was not to the extent of SMT. Challenge with the entomopathogenic Gram-negative bacterium Photorhabdus asymbiotica also enhanced NO production by hemocytes of both stages. SMT, alone or in combination with P. asymbiotica significantly decreased levels of NO production. However, it was observed that phenoloxidase activity (a cascade for innate immune responses) was independent of NO production stimulation. NO donors, S-nitroso-N-acetyl-penicillamine (SNAP) and diethylenetriamine NO adduct (DETA/NO) at various concentrations (100-500 microM) resulted in the lysis of hemocytes dose dependently. The nitrite production in these cases was however similar to LPS stimulation (10 microg/mL) and 1.5-3 fold lower than those observed upon P. asymbiotica (2.5 x 10(7) cfu/mL) stimulation. Survival analysis (Kaplan-Meier) following injection of P. asymbiotica alone or in combination with SMT revealed that only 12.5% (median survival 25.5 h) of co-injected larvae of G. mellonella survived in comparison to 28.6% (median survival 29 h) survivors in P. asymbiotica alone-injected groups till the end of the study. In contrast, co-injected pharate prepupa survived longer (median survival 28 h) than the P. asymbiotica alone-injected individuals (median survival 24 h); however, both co-injected and P. asymbiotica-injected groups showed 100% mortality at the end of the study. Based on the above, we propose that although NO production is involved in cellular immune responses of this insect to bacterial infection it does not appear to be a part of the signalling pathway that initiates the prophenoloxidase (PPO) cascade, and the extended NO production/overproduction by pharate prepupal hemocytes could result in cytotoxic rather than cytoprotective effects compared with larval hemocytes.