Inhibition of soluble epoxide hydrolase (sEH) appears to be promising for the treatment of many diseases. Studies have focused on the beneficial effects of epoxyeicosatrienoic acids (EETs), which are sEH substrates. However, our recent studies have shown that the sEH activity is crucial for the proper intestinal cell differentiation. In this recent study, we investigated the impact of TPPU, an inhibitor of sEH, on the colon cancer cell lines Caco2 and HT-29. We analysed the changes in the expression of the cytoskeletal protein ezrin and the phosphorylated protein kinase p38 (p-p38). Our results showed a decrease in ezrin expression in differentiated cells and an increase in p-p38 expression after TPPU treatment. Immunocytochemical staining revealed a higher staining intensity of p-p38 in the nuclei of HT-29 cells following TPPU treatment. Immunohistochemical staining was performed on human samples of normal colon tissue, grade 2 tumours, and embryonal/foetal tissues. The staining intensity of ezrin in tumours was reduced in the surface area compared to the crypts. Additionally, we observed the translocation of p-p38 expression from the cytoplasm to the nucleus during differentiation. The tumour samples exhibited higher levels of p-p38 in the cytoplasm, similar to normal undifferentiated tissue. To observe the disruption of the cytoskeleton after TPPU treatment, confocal microscopy was used. It was found that β-actin associated with ezrin forms clusters under the plasma membranes. All of these results are significant because sEH inhibitors are being tested in clinical trials, but they could cause an unexpected adverse effects.

• Klíčová slova
• Ezrin, Immunohistochemistry, Intestinal Epithelium, P-p38, Soluble Epoxide Hydrolase, TPPU,
• MeSH
• buněčná diferenciace * účinky léků   MeSH
• buňky HT-29 MeSH
• Caco-2 buňky MeSH
• cytoskeletální proteiny * metabolismus   MeSH
• epoxid hydrolasy * antagonisté a inhibitory   metabolismus   MeSH
• fenylmočovinové sloučeniny farmakologie   MeSH
• inhibitory enzymů farmakologie   MeSH
• lidé MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• nádory tračníku * farmakoterapie   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cytoskeletální proteiny * MeSH
• epoxid hydrolasy * MeSH
• ezrin MeSH Prohlížeč
• fenylmočovinové sloučeniny MeSH
• inhibitory enzymů MeSH
• mitogenem aktivované proteinkinasy p38 MeSH

T cells are pivotal in the adaptive immune defense, necessitating a delicate balance between robust response against infections and self-tolerance. Their activation involves intricate cross-talk among signaling pathways triggered by the T-cell antigen receptors (TCR) and co-stimulatory or inhibitory receptors. The molecular regulation of these complex signaling networks is still incompletely understood. Here, we identify the adaptor protein ABIN1 as a component of the signaling complexes of GITR and OX40 co-stimulation receptors. T cells lacking ABIN1 are hyper-responsive ex vivo, exhibit enhanced responses to cognate infections, and superior ability to induce experimental autoimmune diabetes in mice. ABIN1 negatively regulates p38 kinase activation and late NF-κB target genes. P38 is at least partially responsible for the upregulation of the key effector proteins IFNG and GZMB in ABIN1-deficient T cells after TCR stimulation. Our findings reveal the intricate role of ABIN1 in T-cell regulation.

• Klíčová slova
• ABIN1, Antigen Receptor, Co-stimulation, T Cells, p38,
• MeSH
• adaptorové proteiny signální transdukční * metabolismus   genetika   MeSH
• aktivace lymfocytů imunologie   genetika   MeSH
• cytotoxické T-lymfocyty * imunologie   metabolismus   MeSH
• diabetes mellitus 1. typu imunologie   genetika   metabolismus   MeSH
• glukokortikoidy indukovaný protein související s TNRF MeSH
• interferon gama metabolismus   MeSH
• lidé MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• NF-kappa B metabolismus   MeSH
• receptory antigenů T-buněk metabolismus   MeSH
• receptory OX40 metabolismus   genetika   MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adaptorové proteiny signální transdukční * MeSH
• glukokortikoidy indukovaný protein související s TNRF MeSH
• interferon gama MeSH
• mitogenem aktivované proteinkinasy p38 MeSH
• NF-kappa B MeSH
• receptory antigenů T-buněk MeSH
• receptory OX40 MeSH
• Tnfrsf18 protein, mouse MeSH Prohlížeč

Apoptosis signal-regulating kinase (ASK) 1, a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, modulates diverse responses to oxidative and endoplasmic reticulum (ER) stress and calcium influx. As a crucial cellular stress sensor, ASK1 activates c-Jun N-terminal kinases (JNKs) and p38 MAPKs. Their excessive and sustained activation leads to cell death, inflammation and fibrosis in various tissues and is implicated in the development of many neurological disorders, such as Alzheimer's, Parkinson's and Huntington disease and amyotrophic lateral sclerosis, in addition to cardiovascular diseases, diabetes and cancer. However, currently available inhibitors of JNK and p38 kinases either lack efficacy or have undesirable side effects. Therefore, targeted inhibition of their upstream activator, ASK1, stands out as a promising therapeutic strategy for treating such severe pathological conditions. This review summarizes recent structural findings on ASK1 regulation and its role in various diseases, highlighting prospects for ASK1 inhibition in the treatment of these pathologies.

• Klíčová slova
• 14-3-3, ASK1, MAP kinase, kinase, phosphorylation, protein–protein interaction,
• MeSH
• apoptóza fyziologie   MeSH
• fosforylace MeSH
• JNK mitogenem aktivované proteinkinasy metabolismus   MeSH
• lidé MeSH
• MAP kinasa-kinasa-kinasa 5 genetika   metabolismus   fyziologie   ultrastruktura   MeSH
• MAP kinasový signální systém MeSH
• MAP kinasy kinas (kinas) genetika   metabolismus   MeSH
• mapy interakcí proteinů genetika   fyziologie   MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• oxidace-redukce MeSH
• oxidační stres MeSH
• proteiny 14-3-3 metabolismus   MeSH
• proteiny regulující apoptózu metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• stres endoplazmatického retikula MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• JNK mitogenem aktivované proteinkinasy MeSH
• MAP kinasa-kinasa-kinasa 5 MeSH
• MAP kinasy kinas (kinas) MeSH
• MAP3K5 protein, human MeSH Prohlížeč
• mitogenem aktivované proteinkinasy p38 MeSH
• proteiny 14-3-3 MeSH
• proteiny regulující apoptózu MeSH

Successful navigation of the mouse preimplantation stages of development, during which three distinct blastocyst lineages are derived, represents a prerequisite for continued development. We previously identified a role for p38-mitogen-activated kinases (p38-MAPK) regulating blastocyst inner cell mass (ICM) cell fate, specifically primitive endoderm (PrE) differentiation, that is intimately linked to rRNA precursor processing, polysome formation and protein translation regulation. Here, we develop this work by assaying the role of DEAD-box RNA helicase 21 (DDX21), a known regulator of rRNA processing, in the context of p38-MAPK regulation of preimplantation mouse embryo development. We show nuclear DDX21 protein is robustly expressed from the 16-cell stage, becoming exclusively nucleolar during blastocyst maturation, a localization dependent on active p38-MAPK. siRNA-mediated clonal Ddx21 knockdown within developing embryos is associated with profound cell-autonomous and non-autonomous proliferation defects and reduced blastocyst volume, by the equivalent peri-implantation blastocyst stage. Moreover, ICM residing Ddx21 knockdown clones express the EPI marker NANOG but rarely express the PrE differentiation marker GATA4. These data contribute further significance to the emerging importance of lineage-specific translation regulation, as identified for p38-MAPK, during mouse preimplantation development.

• Klíčová slova
• DDX21, cell fate specification, p38-MAPK, preimplantation embryo development,
• MeSH
• blastocysta cytologie   metabolismus   MeSH
• buněčná diferenciace * genetika   MeSH
• buněčný rodokmen genetika   MeSH
• DEAD-box RNA-helikasy genetika   metabolismus   MeSH
• embryonální vývoj * genetika   MeSH
• fluorescenční protilátková technika MeSH
• genový knockdown MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• myši MeSH
• signální transdukce MeSH
• těhotenství MeSH
• transport proteinů MeSH
• vazba proteinů MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DDX21 protein, mouse MeSH Prohlížeč
• DEAD-box RNA-helikasy MeSH
• mitogenem aktivované proteinkinasy p38 MeSH

Melanoma phenotype plasticity underlies tumour dissemination and resistance to therapy, yet its regulation is incompletely understood. In vivo switching between a more differentiated, proliferative phenotype and a dedifferentiated, invasive phenotype is directed by the tumour microenvironment. We found that treatment of partially dedifferentiated, invasive A375M2 cells with two structurally unrelated p38 MAPK inhibitors, SB2021920 and BIRB796, induces a phenotype switch in 3D collagen, as documented by increased expression of melanocyte differentiation markers and a loss of invasive phenotype markers. The phenotype is accompanied by morphological change corresponding to amoeboid-mesenchymal transition. We performed RNA sequencing with an Illumina HiSeq platform to fully characterise transcriptome changes underlying the switch. Gene expression results obtained with RNA-seq were validated by comparing them with RT-qPCR. Transcriptomic data generated in the study will extend the present understanding of phenotype plasticity in melanoma and its contribution to invasion and metastasis.

• Klíčová slova
• amoeboid invasion, cancer, melanoma, metastasis, phenotype switch,
• MeSH
• buněčná diferenciace účinky léků   genetika   MeSH
• fenotyp MeSH
• genová ontologie MeSH
• imidazoly farmakologie   MeSH
• inhibitory proteinkinas farmakologie   MeSH
• kolagen metabolismus   MeSH
• lidé MeSH
• melanom genetika   patologie   MeSH
• mitogenem aktivované proteinkinasy p38 antagonisté a inhibitory   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádorové mikroprostředí účinky léků   genetika   MeSH
• naftaleny farmakologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• proliferace buněk účinky léků   genetika   MeSH
• pyrazoly farmakologie   MeSH
• pyridiny farmakologie   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• sekvenování transkriptomu metody   MeSH
• stanovení celkové genové exprese metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole MeSH Prohlížeč
• doramapimod MeSH Prohlížeč
• imidazoly MeSH
• inhibitory proteinkinas MeSH
• kolagen MeSH
• mitogenem aktivované proteinkinasy p38 MeSH
• naftaleny MeSH
• pyrazoly MeSH
• pyridiny MeSH

Fusarium-derived mycotoxin deoxynivalenol (DON) usually induces diarrhea, vomiting and gastrointestinal inflammation. We studied the cytotoxic effect of DON on porcine small intestinal epithelium using the intestinal porcine epithelial cell line IPEC-J2. We screened out differentially expressed genes (DEGs) using RNA-seq and identified 320 upregulated genes and 160 downregulated genes. The enrichment pathways of these DEGs focused on immune-related pathways. DON induced proinflammatory gene expression, including cytokines, chemokines and other inflammation-related genes. DON increased IL1A, IL6 and TNF-α release and DON activated the phosphorylation of extracellular signal-regulated kinase-1 and-2 (ERK1/2), JUN N-terminal kinase (JNK) and p38 MAPK. A p38 inhibitor attenuated DON-induced IL6, TNF-α, CXCL2, CXCL8, IL12A, IL1A, CCL20, CCL4 and IL15 production, while an ERK1/2 inhibitor had only a small inhibitory effect on IL15 and IL6. An inhibitor of p38 MAPK decreased the release of IL1A, IL6 and TNF-α and an inhibitor of ERK1/2 partly attenuated protein levels of IL6. These data demonstrate that DON induces proinflammatory factor production in IPEC-J2 cells by activating p38 and ERK1/2.

• Klíčová slova
• IPEC-J2 cells, MAPKs, RNA-seq, deoxynivalenol, inflammation,
• MeSH
• buněčné linie MeSH
• epitelové buňky účinky léků   imunologie   metabolismus   MeSH
• interleukin-1 genetika   MeSH
• interleukin-6 genetika   MeSH
• MAP kinasový signální systém účinky léků   genetika   imunologie   MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• prasata MeSH
• střevní sliznice účinky léků   imunologie   metabolismus   MeSH
• TNF-alfa genetika   MeSH
• transkriptom účinky léků   MeSH
• trichotheceny toxicita   MeSH
• viabilita buněk účinky léků   MeSH
• zánět MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• deoxynivalenol MeSH Prohlížeč
• interleukin-1 MeSH
• interleukin-6 MeSH
• mitogenem aktivované proteinkinasy p38 MeSH
• TNF-alfa MeSH
• trichotheceny MeSH

Changes in ecological and environmental factors lead to an increased occurrence of cyanobacterial water blooms, while secondary metabolites-producing cyanobacteria pose a threat to both environmental and human health. Apart from oral and dermal exposure, humans may be exposed via inhalation and/or swallowing of contaminated water and aerosols. Although many studies deal with liver toxicity, less information about the effects in the respiratory system is available. We investigated the effects of a prevalent cyanotoxin, microcystin-LR (MC-LR), using respiratory system-relevant human bronchial epithelial (HBE) cells. The expression of specific organic-anion-transporting polypeptides was evaluated, and the western blot analysis revealed the formation and accumulation of MC-LR protein adducts in exposed cells. However, MC-LR up to 20 μM neither caused significant cytotoxic effects according to multiple viability endpoints after 48-h exposure, nor reduced impedance (cell layer integrity) over 96 h. Time-dependent increase of putative MC-LR adducts with protein phosphatases was not associated with activation of mitogen-activated protein kinases ERK1/2 and p38 during 48-h exposure in HBE cells. Future studies addressing human health risks associated with inhalation of toxic cyanobacteria and cyanotoxins should focus on complex environmental samples of cyanobacterial blooms and alterations of additional non-cytotoxic endpoints while adopting more advanced in vitro models.

• Klíčová slova
• 16HBE14o-, mitogen-activated protein kinase, HBE1, OATP, cytotoxicity, human bronchial epithelial cells, in vitro, microcystin-LR,
• MeSH
• bronchy cytologie   MeSH
• buněčné linie MeSH
• epitelové buňky účinky léků   metabolismus   MeSH
• extracelulárním signálem regulované MAP kinasy metabolismus   MeSH
• lidé MeSH
• mikrocystiny toxicita   MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• mořské toxiny toxicita   MeSH
• přenašeče organických aniontů genetika   MeSH
• signální transdukce účinky léků   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cyanoginosin LR MeSH Prohlížeč
• extracelulárním signálem regulované MAP kinasy MeSH
• mikrocystiny MeSH
• mitogenem aktivované proteinkinasy p38 MeSH
• mořské toxiny MeSH
• přenašeče organických aniontů MeSH

Bortezomib (BTZ) is used as a chemotherapeutic agent for the treatment of multiple myeloma. Nevertheless, one of the significant limiting complications of BTZ is painful peripheral neuropathy during BTZ therapy. Thus, in this study we examined signaling pathways of interleukin-6 (IL-6) and transient receptor potential ankyrin 1 (TRPA1) in the sensory nerves responsible for neuropathic pain induced by BTZ and further determined if influencing the pathways can improve neuropathic pain. ELISA and western blot analysis were used to examine the levels of IL-6, and IL-6 receptor (IL-6R), TRPA1 and p38-MAPK and JNK signal in the lumbar dorsal root ganglion. Behavioral test was performed to determine mechanical and cold sensitivity in a rat model. Our results showed that systemic injection of BTZ increased mechanical pain and cold sensitivity as compared with control animals. Data also showed that protein expression of TRPA1 and IL-6R was upregulated in the dorsal root ganglion of BTZ rats and blocking TRPA1 attenuated mechanical and cold sensitivity in control rats and BTZ rats. Notably, the inhibitory effect of blocking TRPA1 was smaller in BTZ rats than that in control rats. In addition, a blockade of IL-6 signal attenuated intracellular p38-MAPK and JNK in the sensory neuron. This also decreased TRPA1 expression and alleviated mechanical hyperalgesia and cold hypersensitivity in BTZ rats. In conclusion, we revealed specific signaling pathways leading to neuropathic pain induced by chemotherapeutic BTZ, including IL-6-TRPA1, suggesting that blocking these signals is beneficial to alleviate neuropathic pain during BTZ intervention.

• MeSH
• acetanilidy farmakologie   MeSH
• analgetika farmakologie   MeSH
• bortezomib * MeSH
• chinoxaliny farmakologie   MeSH
• fosforylace MeSH
• inhibitory proteasomu * MeSH
• interleukin-6 antagonisté a inhibitory   metabolismus   MeSH
• JNK mitogenem aktivované proteinkinasy metabolismus   MeSH
• kationtový kanál TRPA1 antagonisté a inhibitory   metabolismus   MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• nervové receptory účinky léků   metabolismus   MeSH
• neuralgie chemicky indukované   farmakoterapie   metabolismus   patofyziologie   MeSH
• potkani Sprague-Dawley MeSH
• práh bolesti účinky léků   MeSH
• puriny farmakologie   MeSH
• pyraziny farmakologie   MeSH
• receptory interleukinu-6 antagonisté a inhibitory   metabolismus   MeSH
• signální transdukce MeSH
• spinální ganglia účinky léků   metabolismus   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide MeSH Prohlížeč
• acetanilidy MeSH
• analgetika MeSH
• bortezomib * MeSH
• chinoxaliny MeSH
• Il6 protein, rat MeSH Prohlížeč
• Il6r protein, rat MeSH Prohlížeč
• inhibitory proteasomu * MeSH
• interleukin-6 MeSH
• JNK mitogenem aktivované proteinkinasy MeSH
• kationtový kanál TRPA1 MeSH
• mitogenem aktivované proteinkinasy p38 MeSH
• puriny MeSH
• pyraziny MeSH
• receptory interleukinu-6 MeSH
• SC 144 MeSH Prohlížeč
• Trpa1 protein, rat MeSH Prohlížeč

Cyanobacterial toxin cylindrospermopsin (CYN) is an emerging freshwater contaminant, whose expanding environmental occurrence might result into increased human health risks. CYN is potent hepatotoxin, with cytotoxicity and genotoxicity documented in primary hepatocytes or hepatoma cell lines. However, there is only limited information about CYN effects on adult human liver stem cells (LSCs), which play an important role in liver tissue development, regeneration and repair. In our study with human liver cell line HL1-hT1 which expresses characteristics of LSCs, CYN was found to be cytotoxic and increasing cell death after 24-48 h exposure to concentrations >1 μM. Subcytotoxic 1 μM concentration did not induce cell death or membrane damage, but inhibited cellular processes related to energy production, leading to a growth stagnation after >72 h. Interestingly, these effects were not associated with increased DNA damage, reactive oxygen species production, or endoplasmic reticulum stress. However, CYN induced a sustained (24-48 h) activation of mitogen-activated protein kinases ERK1/2 and p38, and increased expression of stress-related transcription factor ATF3. Thus, LSCs were not primarily affected by CYN-induced genotoxicity and oxidative stress, but via activation of signaling and transcriptional pathways critical for regulation of cell proliferation, stress responses, cell survival and inflammation. Alterations of LSCs during CYN-induced liver injury, including the role of nongenotoxic mechanisms, should be therefore considered in mechanistic assessments of chronic CYN hepatotoxicity and hepatocarcinogenicity.

• Klíčová slova
• Adult human liver stem cells HL1-hT1, Cylindrospermopsin, DNA damage, Mitogen-activated protein kinases, Nongenotoxic mechanisms, Oxidative stress,
• MeSH
• alkaloidy MeSH
• bakteriální toxiny toxicita   MeSH
• buněčné linie MeSH
• hepatocyty účinky léků   MeSH
• játra metabolismus   MeSH
• kmenové buňky MeSH
• lidé MeSH
• MAP kinasový signální systém MeSH
• mikrocystiny MeSH
• mitogenem aktivovaná proteinkinasa 1 metabolismus   MeSH
• mitogenem aktivovaná proteinkinasa 3 metabolismus   MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• mořské toxiny MeSH
• oxidační stres účinky léků   MeSH
• poškození DNA MeSH
• proliferace buněk MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• testy toxicity MeSH
• toxiny kmene Cyanobacteria MeSH
• uracil analogy a deriváty   toxicita   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alkaloidy MeSH
• bakteriální toxiny MeSH
• cylindrospermopsin MeSH Prohlížeč
• MAPK1 protein, human MeSH Prohlížeč
• mikrocystiny MeSH
• mitogenem aktivovaná proteinkinasa 1 MeSH
• mitogenem aktivovaná proteinkinasa 3 MeSH
• mitogenem aktivované proteinkinasy p38 MeSH
• mořské toxiny MeSH
• reaktivní formy kyslíku MeSH
• toxiny kmene Cyanobacteria MeSH
• uracil MeSH

There are some indications that morphine may exert myocardial protective effects under certain conditions. The aim of the present study was to investigate the effect of morphine on viability and oxidative state of H9c2 cells (rat cardiomyoblasts) influenced by oxidative stress that was elicited by exposure to tert-butyl hydroperoxide (t-BHP). Our experiments showed that pretreatment with morphine before the addition of t-BHP markedly improved cell viability. Morphine was able to increase total antioxidant capacity of H9c2 cells and to reduce the production of reactive oxygen species, protein carbonylation, and lipid peroxidation. Cellular damage caused by t-BHP was associated with low levels of p38 MAPK and GSK-3β phosphorylation. Pretreatment with morphine augmented p38 phosphorylation, and the increased phospho-p38/p38 ratio was preserved even in the presence of t-BHP. Morphine did not change the level of GSK-3β phosphorylation, but interestingly, the phospho-GSK-3β/GSK-3β ratio significantly increased after subsequent incubation with t-BHP. Furthermore, morphine exposure resulted in upregulation of the antioxidant enzyme catalase. The protective effect of morphine was abrogated by the addition of the PI3K inhibitor wortmannin and/or p38 MAPK inhibitor SB203580. It can be concluded that morphine may protect H9c2 cells against oxidative stress and that this protection is at least partially mediated through activation of the p38 MAPK and PI3K/GSK-3β pathways.

• Klíčová slova
• Apoptosis, GSK-3β, H9c2 cells, Morphine, Oxidative stress, Reactive oxygen species, Tert-butyl hydroperoxide, p38 MAPK,
• MeSH
• 1-fosfatidylinositol-3-kinasa metabolismus   MeSH
• antioxidancia farmakologie   MeSH
• apoptóza účinky léků   MeSH
• buněčné linie MeSH
• cytoprotekce MeSH
• fosforylace MeSH
• karbonylace proteinů účinky léků   MeSH
• kardiomyocyty účinky léků   metabolismus   patologie   MeSH
• kinasa glykogensynthasy 3beta metabolismus   MeSH
• krysa rodu Rattus MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• morfin farmakologie   MeSH
• nekróza MeSH
• oxidační stres účinky léků   MeSH
• oxidancia toxicita   MeSH
• peroxidace lipidů účinky léků   MeSH
• signální transdukce účinky léků   MeSH
• terc-butylhydroperoxid toxicita   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1-fosfatidylinositol-3-kinasa MeSH
• antioxidancia MeSH
• Gsk3b protein, rat MeSH Prohlížeč
• kinasa glykogensynthasy 3beta MeSH
• mitogenem aktivované proteinkinasy p38 MeSH
• morfin MeSH
• oxidancia MeSH
• terc-butylhydroperoxid MeSH