Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 32
Filter
Add more filters










Publication year range
1.
Mol Biol (Mosk) ; 57(6): 1017-1027, 2023.
Article in Russian | MEDLINE | ID: mdl-38062957

ABSTRACT

Hsp70 and hydrogen sulfide donors reduce inflammatory processes in human and animal cells. The biological action mediated by Hsp70 and H2S donors (GYY4137 and sodium thiosulfate) depends on their protection kinetics from cell activation by lipopolysaccharides. However, the molecular mechanisms of action of Hsp70 and H2S are not well understood. We studied the effect of human recombinant Hsp70 and H2S donors on the formation of reactive oxygen species and tumor necrosis factor-alpha induced in human cells (THP-1) by lipopolysaccharides. Transcriptomic changes occurring in these cells after LPS administration in combination with GYY4137 pretreatment were investigated. The results we obtained showed that Hsp70 and hydrogen sulfide donors reduce inflammatory processes in cells activated by the action of LPS. Hsp70 and H2S donors differed in the kinetics of the protective action, while hydrogen sulfide donors turned out to be more effective. The role of endocytosis in the mechanisms of protection of cells by H2S and Hsp70 donors from the action of LPS was studied. It has been found that GYY4137 pretreatment of LPS-exposed cells reduces the LPS-induced induction of various pro-inflammatory genes and affects the expression of genes of various intracellular signaling pathways.


Subject(s)
Endocytosis , HSP70 Heat-Shock Proteins , Hydrogen Sulfide , Inflammation , Animals , Humans , Hydrogen Sulfide/pharmacology , Lipopolysaccharides/toxicity , Macrophages/metabolism , HSP70 Heat-Shock Proteins/metabolism , THP-1 Cells/metabolism , Inflammation/chemically induced , Inflammation/metabolism
2.
Mol Biol (Mosk) ; 54(6): 1018-1028, 2020.
Article in Russian | MEDLINE | ID: mdl-33276365

ABSTRACT

The effects of exogenous recombinant human heat shock protein Hsp70 and hydrogen sulfide donor GYY4137 on the mechanisms of endocytosis of lipopolysaccharide (LPS) by human neuroblastoma cells SH-SY5Ywas studied. Hsp70 and GYY4137 have been shown to significantly reduce LPS-induced production of inflammatory mediators by SH-SY5Y cells, including reactive oxygen species, nitric oxide, TNFα, IL-1ß, and IL-6. Both the recombinant protein Hsp70 and the hydrogen sulfide donor GYY4137 exhibited significant protective effects; however, the combined use of these agents did not lead to a cumulative effect. It has been shown that pinocytosis, as well as clathrin-, caveolin-, tubulin- and receptor-dependent endocytosis were involved in protecting the cells by both the hydrogen sulfide donor and Hsp70 from LPS-induced production of reactive oxygen species and NO.


Subject(s)
HSP70 Heat-Shock Proteins/metabolism , Hydrogen Sulfide , Morpholines/pharmacology , Organothiophosphorus Compounds/pharmacology , Cell Line, Tumor , Cytokines , Humans , Hydrogen Sulfide/pharmacology , Lipopolysaccharides/pharmacology , Reactive Oxygen Species/metabolism , Recombinant Proteins/metabolism
3.
Mol Biol (Mosk) ; 54(1): 128-136, 2020.
Article in Russian | MEDLINE | ID: mdl-32163396

ABSTRACT

Neuroinflammation plays a key role in the pathogenesis of neurodegenerative diseases. Microglial cells are the main immune cells of the central nervous system. On exposure to lipopolysaccharides (LPS, components of the cell wall of Gram-negative enterobacteria), microglia is activated to produce reactive oxygen species (ROS), cytokines, and inflammatory mediators, which may cause neuron death. Exogenous recombinant human heat shock protein 70 (HSP70) was tested for effect on the activation of human microglial and neuroblastoma cells in response to LPS from Escherichia coli. Experiments included cell cultivation separately and transferring the conditioned medium from A-172 microglial cells to SK-N-SH neuroblastoma cells to simulate the effect of microglia treated with LPS and/or HSP70. The levels of ROS, TNFα, and apoptosis in LPS-treated cells were estimated in the presence or absence of HSP70. HSP70 was found to reduce the LPS-induced ROS generation, TNFα production, apoptosis, and necrosis, in both separate cell cultures and neuroblastoma cells grown in the conditioned medium from microglial cells. Signaling pathways involving protein kinases p38MAPK, JNK, and PI3K were demonstrated to play an important role in HSP70-mediated protection of microglial and neuroblastoma cells from LPS-induced apoptosis and ROS production.


Subject(s)
Culture Media, Conditioned/chemistry , HSP70 Heat-Shock Proteins/pharmacology , Lipopolysaccharides/toxicity , Neuroblastoma/drug therapy , Neuroprotection/drug effects , Neuroprotective Agents/pharmacology , Signal Transduction/drug effects , Apoptosis/drug effects , Culture Media, Conditioned/pharmacology , Humans , Lipopolysaccharides/immunology , Microglia/drug effects , Microglia/immunology , Microglia/metabolism , Neuroblastoma/metabolism , Neuroblastoma/pathology , Reactive Oxygen Species/metabolism
4.
Inflamm Res ; 69(5): 481-495, 2020 May.
Article in English | MEDLINE | ID: mdl-32157318

ABSTRACT

BACKGROUND: Hydrogen sulfide donors reduce inflammatory signaling in vitro and in vivo. The biological effect mediated by H2S donors depends on the kinetics of the gas release from the donor molecule. However, the molecular mechanisms of H2S-induced immunomodulation were poorly addressed. Here, we studied the effect of two different hydrogen sulfide (H2S)-producing agents on the generation of the LPS-induced inflammatory mediators. Importantly, we investigated the transcriptomic changes that take place in human cells after the LPS challenge, combined with the pretreatment with a slow-releasing H2S donor-GYY4137. METHODS: We investigated the effects of GYY4137 and sodium hydrosulfide on the release of proinflammatory molecules such as ROS, NO and TNF-α from LPS-treated human SH-SY5Y neuroblastoma and the THP-1 promonocytic cell lines. Transcriptomic and RT-qPCR studies using THP-1 cells were performed to monitor the effects of the GYY4137 on multiple signaling pathways, including various immune-related and proinflammatory genes after combined action of LPS and GYY4137. RESULTS: The GYY4137 and sodium hydrosulfide differed in the ability to reduce the production of the LPS-evoked proinflammatory mediators. The pre-treatment with GYY4137 resulted in a drastic down-regulation of many TNF-α effectors that are induced by LPS treatment in THP-1 cells. Furthermore, GYY4137 pretreatment of LPS-exposed cells ameliorates the LPS-mediated induction of multiple pro-inflammatory genes and decreases expression of immunoproteasome genes. Besides, in these experiments we detected the up-regulation of several important pathways that are inhibited by LPS. CONCLUSION: Based on the obtained results we believe that our transcriptomic analysis significantly contributes to the understanding of the molecular mechanisms of anti-inflammatory and cytoprotective activity of hydrogen sulfide donors, and highlights their potential against LPS challenges and other forms of inflammation.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Hydrogen Sulfide/metabolism , Inflammation/metabolism , Morpholines/pharmacology , Organothiophosphorus Compounds/pharmacology , Sulfides/pharmacology , Cell Line , Cytokines/metabolism , Humans , Inflammation/chemically induced , Inflammation/genetics , Lipopolysaccharides , Nitric Oxide/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Transcriptome/drug effects
5.
Mol Biol (Mosk) ; 53(1): 101-108, 2019.
Article in Russian | MEDLINE | ID: mdl-30895957

ABSTRACT

Lipopolysaccharides (LPS), components of the cell wall of gram-negative bacteria, activate neutrophils that trigger pathological processes, including gram-negative sepsis. LPS inhibit spontaneous apoptosis of neutrophils that leads to inflammation. In this work we tested the action of H2S donor (GYY4137) on the activation of human neutrophils by E. coli LPS. We estimated the changes in redox status (ROS level, intracellularglutathione, NO), apoptosis and mitochondrial potential of neutrophils under the LPS action in the presence and absence of GYY4137. GYY4137 reduces the ROS level, slightly reduces GSH, does not influence the NO level and has no apoptogenic effect. LPS induce the increasing of ROS level and inhibit spontaneous apoptosis of neutrophils. We found that GYY4137 prevents the growth of ROS caused by LPS and leads to a reduction of LPS-induced inhibition of neutrophil apoptosis. Thus the mechanism of GYY4137 protection against inflammation, triggered by bacterial infection, is concerned with the neutralization of LPS effect on neutrophils.


Subject(s)
Apoptosis , Hydrogen Sulfide/pharmacology , Morpholines/pharmacology , Neutrophils/drug effects , Organothiophosphorus Compounds/pharmacology , Cells, Cultured , Escherichia coli , Humans , Inflammation , Lipopolysaccharides , Nitric Oxide/metabolism , Reactive Oxygen Species/metabolism
6.
Mol Biol (Mosk) ; 52(4): 683-691, 2018.
Article in Russian | MEDLINE | ID: mdl-30113034

ABSTRACT

Intact amyloid-ß peptides (Aß) may undergo prion-like aggregation when they interact with chemically or structurally modified variants of Aß present in extracellular pathohistological inclusions (amyloid plaques). This aggregation is regarded as one of the key molecular mechanisms of Alzheimer's disease (AD) pathogenesis. Zinc ions are involved in the pathological dimerization and oligomerization of natural Aß isoforms, and zinc-induced oligomers can also initiate the pathological aggregation of Aß. Based on the earlier found molecular mechanism of zinc-dependent oligomerization of Aß, it has been suggested that the targeted inhibition of the 11EVHH14 site in one Aß molecule from zinc-mediated interactions with the same site of another Aß molecule can effectively inhibit the oligomerization and aggregation of Aß. Taking into account the similarity in the structural organization of zinc-binding sites within Aß and angiotensin-converting enzyme (ACE), we hypothesized that inhibitors of the ACE active sites could specifically interact with the 11EVHH14 site of Aß. Using a surface plasmon resonance biosensor and nuclear magnetic resonance spectroscopy, we have found that the ACE inhibitor enalaprilat effectively inhibits zinc-dependent dimerization of the metal-binding domains of intact Aß and Aß with isomerized Asp7 (isoAß). We have also found that enalaprilat protects SH-SY5Y human neuroblastoma cells from the toxic effects of Aß(1-42) and isoAß(1-42), which are among the most common components of amyloid plaques. The results confirm the role of zincdependent oligomerization of Aß in AD pathogenesis and make it possible one to consider enalaprilat as a prototype of antiaggregation agents for treating AD.


Subject(s)
Alzheimer Disease/drug therapy , Amyloid beta-Peptides/genetics , Enalaprilat/pharmacology , Plaque, Amyloid/drug therapy , Protein Aggregation, Pathological/drug therapy , Alzheimer Disease/genetics , Alzheimer Disease/pathology , Amyloid beta-Peptides/antagonists & inhibitors , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Binding Sites/drug effects , Biosensing Techniques , Cell Line, Tumor , Humans , Magnetic Resonance Spectroscopy , Neuroblastoma/drug therapy , Plaque, Amyloid/genetics , Plaque, Amyloid/pathology , Protein Aggregation, Pathological/genetics , Protein Aggregation, Pathological/pathology , Protein Binding/drug effects , Protein Isoforms/antagonists & inhibitors , Protein Isoforms/genetics , Protein Multimerization/drug effects , Surface Plasmon Resonance , Zinc/chemistry
7.
Sci Rep ; 8(1): 3518, 2018 02 23.
Article in English | MEDLINE | ID: mdl-29476081

ABSTRACT

Neuronal dysfunction and loss associated with the accumulation of amyloid-ß (Aß) in the form of extracellular amyloid plaques and hyperphosphorylated tau in the form of intraneuronal neurofibrillary tangles represent key features of Alzheimer's disease (AD). Amyloid plaques found in the brains of AD patients are predominantly composed of Aß42 and its multiple chemically or structurally modified isoforms. Recently, we demonstrated that Aß42 with isomerised Asp7 (isoAß42) which is one of the most abundant Aß isoform in plaques, exhibited high neurotoxicity in human neuronal cells. Here, we show that, in SH-SY5Y neuroblastoma cells, the administration of synthetic isoAß42 rather than intact Aß42 resulted in a significantly higher level of protein phosphorylation, especially the phosphorylation of tau, tubulins, and matrin 3. IsoAß42 induced a drastic reduction of tau protein levels. Our data demonstrate, for the first time, that isoAß42, being to date the only known synthetic Aß species to cause AD-like amyloidogenesis in an animal AD model, induced cell death by disabling structural proteins in a manner characteristic of that observed in the neurons of AD patients. The data emphasize an important role of isoAß42 in AD progression and provide possible neurotoxicity paths for this particular isoform.


Subject(s)
Amyloid beta-Peptides/toxicity , Aspartic Acid/metabolism , Neurons/drug effects , Peptide Fragments/toxicity , Phosphoserine/metabolism , Protein Processing, Post-Translational , tau Proteins/metabolism , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Apoptosis/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Electrophoresis, Gel, Two-Dimensional , Humans , Models, Biological , Neurons/metabolism , Neurons/pathology , Nuclear Matrix-Associated Proteins/genetics , Nuclear Matrix-Associated Proteins/metabolism , Phosphorylation , Protein Isoforms/toxicity , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Tubulin/genetics , Tubulin/metabolism , tau Proteins/genetics
8.
Mol Biol (Mosk) ; 52(6): 1082-1092, 2018.
Article in Russian | MEDLINE | ID: mdl-30633251

ABSTRACT

The accumulation and aggregation of ß-amyloids are major molecular events underlying the progression of Alzheimer's disease. In neural cells, recombinant HSP70 reduces the toxic effect of Aß and its isomeric forms. Here we describe the proteome of the neuroblastoma cell line after incubation with amyloid peptides Aß42 and isomerized Asp7 (isoAß42) without and with human recombinant heat shock protein 70 (HSP70). Incubation of SH-SY5Y cell culture with the synthetic Aß-peptides leads to a decrease in the levels of several cytoskeleton proteins (e.g., ACTN1, VIME, TPM3) and several chaperonines involved in the folding of actin and tubulin (TCPQ, TCPG, TCPE, TCPB). These changes are accompanied by an increase in the expression of calmodulin and the proteins involved in folding in the endoplasmic reticulum and endoplasmic cell stress response. The presence of exogenous HSP70 has led to an increase in expression of several chaperones and a few other proteins including endogenous HSP70. A combined effect of recombinant HSP70 with Aß peptides reduced cell apoptosis and significantly decreased the level of tubulin phosphorylation caused by the addition of Aß peptides.


Subject(s)
Amyloid beta-Peptides/metabolism , HSP70 Heat-Shock Proteins/metabolism , Neuroblastoma/metabolism , Proteome , Cell Line, Tumor , Humans , Peptide Fragments
9.
Mol Biol (Mosk) ; 51(1): 166-171, 2017.
Article in Russian | MEDLINE | ID: mdl-28251980

ABSTRACT

Experimental evidences indicate that heat-shock protein 70 (HSP70) can serve as a prospective therapeutic agent to treat Alzheimer's disease (AD). It has demonstrated a neuroprotective effect in vivo on mice models of AD. Moreover, HSP70 decreases oxidative stress in neurons induced by amyloid-ß (Aß42) and its more toxic form with isomerized Asp7 (isoAß42). The dysfunction of Ubiquitin-proteasome system (UPS) is observed in AD. UPS is responsible for the degradation of the majority of cellular proteins and plays an important role in protecting cells from oxidative stress. Here, we have shown that the incubation of human neuroblastoma cells SK-N-SH with isoAß42 increases the activity of intracellular proteasomes, which are the principal elements of the UPS. On the contrary, the proteasomal activity was decreased in isoAß42-treated cells in the presence of exogenous HSP70. These results highlight the existence of an interplay between Aß peptides, proteasomes, and HSP70.


Subject(s)
HSP70 Heat-Shock Proteins/pharmacology , Neuroblastoma , Proteasome Endopeptidase Complex/metabolism , Alzheimer Disease , Amyloid beta-Peptides , Animals , Cell Line, Tumor , Humans , Mice , Peptide Fragments
11.
Cell Stress Chaperones ; 22(1): 163-171, 2017 01.
Article in English | MEDLINE | ID: mdl-27783274

ABSTRACT

Human heat shock protein Hsp70 was experimentally inserted into polyelectrolyte microcapsules. Encapsulated recombinant Hsp70 was studied in terms of its effects on neutrophil apoptosis, the production of reactive oxygen species, and the secretion of tumor necrosis factor alpha by promonocytic THP-1 cells. It was found that encapsulated Hsp70 effectively inhibits neutrophil apoptosis, unlike free exogenous protein used in solution. In THP-1 cells, encapsulated and free Hsp70 reduced LPS-induced tumor necrosis factor alpha production with a similar efficiency. Encapsulated Hsp70 reduces LPS-induced reactive oxygen species production by neutrophils in the course of its release from the microcapsules but not as much as free Hsp70. Thus, the polyelectrolyte microcapsules can be used as containers for the effective delivery of Hsp70 to neutrophils and monocytes to significantly improve the functioning of the innate immune system.


Subject(s)
HSP70 Heat-Shock Proteins/metabolism , Lipopolysaccharides/toxicity , Phagocytes/drug effects , Reactive Oxygen Species/metabolism , Tumor Necrosis Factor-alpha/metabolism , Cells, Cultured , HSP70 Heat-Shock Proteins/genetics , Humans , Microscopy, Confocal , Monocytes/cytology , Monocytes/drug effects , Monocytes/metabolism , Neutrophils/cytology , Neutrophils/drug effects , Neutrophils/metabolism , Recombinant Proteins/biosynthesis , Recombinant Proteins/isolation & purification
12.
Dokl Biochem Biophys ; 469(1): 239-43, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27599502

ABSTRACT

The effect of exogenous heat shock protein HSP70 and lipopolysaccharide (LPS) on the production of reactive oxygen species (ROS), TNFα secretion, and mRNA expression by human neuroblastoma SK-N-SH cells. It was shown that exogenous HSP70 protects neuroblastoma cells from the action of LPS. The protection mechanism of HSP70 includes a reduction in the production of ROS and TNFα and a decrease in the expression of TLR4 and IL-1ß mRNA in SK-N-SH cells induced by LPS.


Subject(s)
HSP70 Heat-Shock Proteins/pharmacology , Immunologic Factors/pharmacology , Lipopolysaccharides/toxicity , Neuroblastoma/drug therapy , Neuroblastoma/immunology , Recombinant Proteins/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/physiology , HSP70 Heat-Shock Proteins/genetics , Humans , Interleukin-1beta/metabolism , Nitric Oxide Synthase Type II/metabolism , RNA, Messenger/metabolism , Reactive Oxygen Species/metabolism , Recombinant Proteins/genetics , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 4/metabolism , Tumor Necrosis Factor-alpha/metabolism
13.
Mol Biol (Mosk) ; 50(6): 1053-1056, 2016.
Article in Russian | MEDLINE | ID: mdl-28064323

ABSTRACT

The progress of neurodegeneration in Alzheimer's disease is closely associated with inflammatory processes in the brain tissues induced by beta-amyloid peptides (Aß). In this paper, we showed that Aß(1-42) and isoAß(1-42) in human neuroblastoma cells SK-N-SH and promonocyte THP-1 activated the production of tumor necrosis factor (TNFα). Notably, isoAß(1-42) had the strongest effect on the increase in the level of TNFα. The addition of recombinant heat-shock protein HSP70 reduces TNFα production induced by Aß, which leads to a decrease in neuronal cell damage at the organism level.


Subject(s)
Amyloid beta-Peptides/metabolism , HSP70 Heat-Shock Proteins/metabolism , Monocytes/metabolism , Neoplasm Proteins/metabolism , Neuroblastoma/metabolism , Peptide Fragments/metabolism , Tumor Necrosis Factor-alpha/metabolism , Animals , Cell Line, Tumor , Coculture Techniques , Humans , Mice , Monocytes/pathology , Neuroblastoma/pathology
14.
Mol Biol (Mosk) ; 49(6): 1030-4, 2015.
Article in Russian | MEDLINE | ID: mdl-26710786

ABSTRACT

Neuronal cell death in Alzheimer's disease is associated with the development of oxidative stress caused by the reactive oxygen species (ROS), which can be generated as a result of the effect of beta-amyloid peptides. One of the sources of ROS is hydrogen peroxide, inducing the apoptosis and necrosis of neural tissue cells. The mechanism of hydrogen peroxide apoptotic action includes launching signaling pathways that involve protein kinases PI3K, p38MAPK, JNK and ERK. Oxidative stress leads to increased synthesis of heat-shock proteins in the cells including HSP70. It was shown that the exogenous HSP70 could reduce generation of ROS in cells. In this study, we determined how HSP70 affected apoptosis and necrosis in human neuroblastoma cells SK-N-SH, induced by hydrogen peroxide and ß-amyloid peptide Aß(1-42). It was shown that HSP70 reduces the cytotoxic effects of hydrogen peroxide and beta-amyloid, and protein kinases PI3K and JNK play an important role in the mechanism of HSP70 protective effect on the peroxide induced apoptosis in SK-N-SH cells.


Subject(s)
Amyloid beta-Peptides/toxicity , HSP70 Heat-Shock Proteins/pharmacology , Neuroblastoma/metabolism , Neuroprotective Agents/pharmacology , Peptide Fragments/toxicity , Apoptosis/drug effects , Cell Line, Tumor , Humans , Hydrogen Peroxide/toxicity , Oxidative Stress
16.
Dokl Biol Sci ; 465(1): 299-302, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26725241

ABSTRACT

Microencapsulated heat shock proteins HSP 70 were studied in terms of their effects on neutrophil apoptosis, production of reactive oxygen species, and secretion of TNF-α by human neurtrophils and monocytes. Encapsulated HSP70 inhibited neutrophil apoptosis by 65% as compared to the effect of nonencapsulated HSP70; TNF-α production by the promonocytic THP-1 cells was similarly inhibited by the non-encapsulated and encapsulated HSP70. Thus, the polyelectrolyte micromolecules can be used as containers for effective delivery of HSP70 up to neutrophils and monocytes to correct the innate immunity functions.


Subject(s)
Drug Delivery Systems , HSP70 Heat-Shock Proteins/administration & dosage , Phagocytes/drug effects , Tumor Necrosis Factor-alpha/metabolism , Apoptosis/drug effects , Cell Line , Drug Compounding , HSP70 Heat-Shock Proteins/chemistry , Humans , Immunity, Innate/drug effects , Monocytes/drug effects , Neutrophils/drug effects , Reactive Oxygen Species/metabolism
18.
Vestn Ross Akad Med Nauk ; (9-10): 10-4, 2014.
Article in Russian | MEDLINE | ID: mdl-25816637

ABSTRACT

OBJECTIVE: Our aim was to study the effect of calf blood gemodializat on apoptosis and intracellular signaling pathways of neuroblastoma cells SK-N-SH human. METHODS: Apoptosis was recorded by fluorescent microscopy using Hoechst 33342. Necrosis cells was monitored by propidium iodide. The fluorescence of the cells was recorded on a fluorescence inverted microscope Keyence BZ8100 (Japan). Formation of reactive oxygen species (ROS) in the cells of SK-N-SH was determined using nitroblue tetrazolium by absorbance at 620 nm on a plate reader "Uniplan". RESULTS: When adding hydrogen peroxide to the background of the calf blood gemodializat been decreasing apoptosis of these cells with 43 to 17% relative to apoptosis in the presence of a hydrogen peroxide. Under these conditions, the calf blood gemodializat significantly reduced ROS formation in human neuroblastoma cells SK-N-SH by the action of hydrogen peroxide. In these cells, we investigated the influence of calf blood gemodializat on apoptosis and intracellular signaling pathway involving mitogen-activated protein kinase (p38MAPK), extracellular regulatory kinase (ERK), phosphatidylinositol 3-kinase (PI-3K) and-Jun-N-terminal kinase (JNK) using their selective inhibitors. CONCLUSION: It was shown that the mechanism of the protective effect of calf blood gemodializat against peroxide-induced apoptosis in SK-N-SH dominant role is played by p38 MAPK and PI-3K.


Subject(s)
Hydrogen Peroxide/toxicity , Neuroblastoma/drug therapy , Renal Dialysis , Animals , Apoptosis/drug effects , Cattle , Cell Line, Tumor , Enzyme Inhibitors/pharmacology , Flavonoids/pharmacology , Humans , Imidazoles/pharmacology , MAP Kinase Kinase 4/antagonists & inhibitors , MAP Kinase Kinase 4/metabolism , Neuroblastoma/metabolism , Neuroblastoma/pathology , Neurotoxicity Syndromes/pathology , Phosphatidylinositol 3-Kinase/metabolism , Pyridines/pharmacology , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , p38 Mitogen-Activated Protein Kinases/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...