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Article: Role of Mitogen-Activated Protein (MAP) Kinase Pathways in Metabolic Diseases.

Ng, Gavin Yong Quan / Loh, Zachary Wai-Loon / Fann, David Y / Mallilankaraman, Karthik / Arumugam, Thiruma V / Hande, M Prakash

Genome integrity

2024 Volume 15, Page(s) e20230003

Abstract: ... by a myriad of signalling pathways. Mammalian mitogen-activated protein (MAP) kinases constitute one ... stress responses, as well as inflammation. This evolutionarily conserved MAP kinase signalling arm is ... MAP kinase signalling in the development of metabolic diseases, highlighting the potential therapeutic ...

Abstract	Physiological processes that govern the normal functioning of mammalian cells are regulated by a myriad of signalling pathways. Mammalian mitogen-activated protein (MAP) kinases constitute one of the major signalling arms and have been broadly classified into four groups that include extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), p38, and ERK5. Each signalling cascade is governed by a wide array of external and cellular stimuli, which play a critical part in mammalian cells in the regulation of various key responses, such as mitogenic growth, differentiation, stress responses, as well as inflammation. This evolutionarily conserved MAP kinase signalling arm is also important for metabolic maintenance, which is tightly coordinated via complicated mechanisms that include the intricate interaction of scaffold proteins, recognition through cognate motifs, action of phosphatases, distinct subcellular localisation, and even post-translational modifications. Aberration in the signalling pathway itself or their regulation has been implicated in the disruption of metabolic homeostasis, which provides a pathophysiological foundation in the development of metabolic syndrome. Metabolic syndrome is an umbrella term that usually includes a group of closely associated metabolic diseases such as hyperglycaemia, hyperlipidaemia, and hypertension. These risk factors exacerbate the development of obesity, diabetes, atherosclerosis, cardiovascular diseases, and hepatic diseases, which have accounted for an increase in the worldwide morbidity and mortality rate. This review aims to summarise recent findings that have implicated MAP kinase signalling in the development of metabolic diseases, highlighting the potential therapeutic targets of this pathway to be investigated further for the attenuation of these diseases.
Language	English
Publishing date	2024-01-17
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2556795-0
ISSN	2041-9414
ISSN	2041-9414
DOI	10.14293/genint.14.1.004
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Article ; Online: Cannabinoid Mixture Affects the Fate and Functions of B Cells through the Modulation of the Caspase and MAP Kinase Pathways.

Lampron, Marie-Claude / Paré, Isabelle / Al-Zharani, Mohammed / Semlali, Abdelhabib / Loubaki, Lionel

Cells

2023 Volume 12, Issue 4

Abstract: ... 3 µg/mL). In addition, the activation of MAP Kinase, STATs, and the NF-κB pathway and the number ... caspase activation, and the activation of key signaling pathways (ERK1/2, NF-κB, STAT5, and p38 ...

Abstract	Cannabis use is continuously increasing in Canada, raising concerns about its potential impact on immunity. The current study assessed the impact of a cannabinoid mixture (CM) on B cells and the mechanisms by which the CM exerts its potential anti-inflammatory properties. Peripheral blood mononuclear cells (PBMCs) were treated with different concentrations of the CM to evaluate cytotoxicity. In addition, flow cytometry was used to evaluate oxidative stress, antioxidant levels, mitochondrial membrane potential, apoptosis, caspase activation, and the activation of key signaling pathways (ERK1/2, NF-κB, STAT5, and p38). The number of IgM- and IgG-expressing cells was assessed using FluoroSpot, and the cytokine production profile of the B cells was explored using a cytokine array. Our results reveal that the CM induced B-cell cytotoxicity in a dose-dependent manner, which was mediated by apoptosis. The levels of ROS and those of the activated caspases, mitochondrial membrane potential, and DNA damage increased following exposure to the CM (3 µg/mL). In addition, the activation of MAP Kinase, STATs, and the NF-κB pathway and the number of IgM- and IgG-expressing cells were reduced following exposure to the CM. Furthermore, the exposure to the CM significantly altered the cytokine profile of the B cells. Our results suggest that cannabinoids have a detrimental effect on B cells, inducing caspase-mediated apoptosis.
MeSH term(s)	Caspases/metabolism ; NF-kappa B/metabolism ; Cannabinoids ; Leukocytes, Mononuclear/metabolism ; Mitogen-Activated Protein Kinases/metabolism ; Cytokines ; Immunoglobulin G ; Immunoglobulin M
Chemical Substances	Caspases (EC 3.4.22.-) ; NF-kappa B ; Cannabinoids ; Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Cytokines ; Immunoglobulin G ; Immunoglobulin M
Language	English
Publishing date	2023-02-11
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12040588
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Article ; Online: Deficiency in Retinal TGFβ Signaling Aggravates Neurodegeneration by Modulating Pro-Apoptotic and MAP Kinase Pathways.

Bielmeier, Christina B / Schmitt, Sabrina I / Kleefeldt, Nikolai / Boneva, Stefaniya K / Schlecht, Anja / Vallon, Mario / Tamm, Ernst R / Hillenkamp, Jost / Ergün, Süleyman / Neueder, Andreas / Braunger, Barbara M

International journal of molecular sciences

2022 Volume 23, Issue 5

Abstract: Transforming growth factor β (TGFβ) signaling has manifold functions such as regulation of cell growth, differentiation, migration, and apoptosis. Moreover, there is increasing evidence that it also acts in a neuroprotective manner. We recently showed ... ...

Abstract	Transforming growth factor β (TGFβ) signaling has manifold functions such as regulation of cell growth, differentiation, migration, and apoptosis. Moreover, there is increasing evidence that it also acts in a neuroprotective manner. We recently showed that TGFβ receptor type 2 (
MeSH term(s)	Animals ; Disease Models, Animal ; Ependymoglial Cells/metabolism ; Mice ; Mitogen-Activated Protein Kinases/metabolism ; Receptor, Transforming Growth Factor-beta Type II/genetics ; Receptor, Transforming Growth Factor-beta Type II/metabolism ; Retina/metabolism ; Retinal Degeneration/genetics ; Retinal Degeneration/metabolism ; Transforming Growth Factor beta/metabolism
Chemical Substances	Transforming Growth Factor beta ; Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Receptor, Transforming Growth Factor-beta Type II (EC 2.7.11.30)
Language	English
Publishing date	2022-02-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23052626
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Article ; Online: Regulation of biotic interactions and responses to abiotic stresses by MAP kinase pathways in plant pathogenic fungi.

Zhang, Xue / Wang, Zeyi / Jiang, Cong / Xu, Jin-Rong

Stress biology

2021 Volume 1, Issue 1, Page(s) 5

Abstract: Like other eukaryotes, fungi use MAP kinase (MAPK) pathways to mediate cellular changes responding ... to external stimuli. In the past two decades, three well-conserved MAP kinase pathways have been characterized ... homologous to the yeast pheromone response and filamentation pathways. In plant pathogens, the IG pathway ...

Abstract	Like other eukaryotes, fungi use MAP kinase (MAPK) pathways to mediate cellular changes responding to external stimuli. In the past two decades, three well-conserved MAP kinase pathways have been characterized in various plant pathogenic fungi for regulating responses and adaptations to a variety of biotic and abiotic stresses encountered during plant infection or survival in nature. The invasive growth (IG) pathway is homologous to the yeast pheromone response and filamentation pathways. In plant pathogens, the IG pathway often is essential for pathogenesis by regulating infection-related morphogenesis, such as appressorium formation, penetration, and invasive growth. The cell wall integrity (CWI) pathway also is important for plant infection although the infection processes it regulates vary among fungal pathogens. Besides its universal function in cell wall integrity, it often plays a minor role in responses to oxidative and cell wall stresses. Both the IG and CWI pathways are involved in regulating known virulence factors as well as effector genes during plant infection and mediating defenses against mycoviruses, bacteria, and other fungi. In contrast, the high osmolarity growth (HOG) pathway is dispensable for virulence in some fungi although it is essential for plant infection in others. It regulates osmoregulation in hyphae and is dispensable for appressorium turgor generation. The HOG pathway also plays a major role for responding to oxidative, heat, and other environmental stresses and is overstimulated by phenylpyrrole fungicides. Moreover, these three MAPK pathways crosstalk and coordinately regulate responses to various biotic and abiotic stresses. The IG and CWI pathways, particularly the latter, also are involved in responding to abiotic stresses to various degrees in different fungal pathogens, and the HOG pathway also plays a role in interactions with other microbes or fungi. Furthermore, some infection processes or stress responses are co-regulated by MAPK pathways with cAMP or Ca
Language	English
Publishing date	2021-08-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ISSN	2731-0450
ISSN (online)	2731-0450
DOI	10.1007/s44154-021-00004-3
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Article ; Online: TOR and MAP kinase pathways synergistically regulate autophagy in response to nutrient depletion in fission yeast.

Corral-Ramos, Cristina / Barrios, Rubén / Ayté, José / Hidalgo, Elena

Autophagy

2021 Volume 18, Issue 2, Page(s) 375–390

Abstract: General autophagy is an evolutionarily conserved process in eukaryotes, by which intracellular materials are transported into and degraded inside lysosomes or vacuoles, with the main goal of recycling those materials during periods of starvation. The ... ...

Abstract	General autophagy is an evolutionarily conserved process in eukaryotes, by which intracellular materials are transported into and degraded inside lysosomes or vacuoles, with the main goal of recycling those materials during periods of starvation. The molecular bases of autophagy have been widely described in
MeSH term(s)	Autophagy ; Leucine/metabolism ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mechanistic Target of Rapamycin Complex 2/metabolism ; Mitogen-Activated Protein Kinases/metabolism ; Nutrients ; Saccharomyces cerevisiae/metabolism ; Schizosaccharomyces/metabolism ; Schizosaccharomyces pombe Proteins/metabolism ; TOR Serine-Threonine Kinases/metabolism
Chemical Substances	Schizosaccharomyces pombe Proteins ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Mechanistic Target of Rapamycin Complex 2 (EC 2.7.11.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Leucine (GMW67QNF9C)
Language	English
Publishing date	2021-06-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2454135-7
ISSN	1554-8635 ; 1554-8627
ISSN (online)	1554-8635
ISSN	1554-8627
DOI	10.1080/15548627.2021.1935522
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Article: Luteolin inhibits proliferation, triggers apoptosis and modulates Akt/mTOR and MAP kinase pathways in HeLa cells.

Raina, Ritu / Pramodh, Sreepoorna / Rais, Naushad / Haque, Shafiul / Shafarin, Jasmin / Bajbouj, Khuloud / Hamad, Mawieh / Hussain, Arif

Oncology letters

2021 Volume 21, Issue 3, Page(s) 192

Abstract: Flavonoids, a subclass of polyphenols, have been shown to be effective against several types of cancer, by decreasing proliferation and inducing apoptosis. Therefore, the aim of the present study was to assess the anti-carcinogenic potential of luteolin ... ...

Abstract	Flavonoids, a subclass of polyphenols, have been shown to be effective against several types of cancer, by decreasing proliferation and inducing apoptosis. Therefore, the aim of the present study was to assess the anti-carcinogenic potential of luteolin on HeLa human cervical cancer cells, through the use of a cell viability assay, DNA fragmentation assay, mitochondrial membrane potential assay, cell cycle analysis using Annexin/PI staining and flow cytometry, gene expression analysis and a protein profiling array. Luteolin treatment exhibited cytotoxicity towards HeLa cells in a dose- and time-dependent manner, and its anti-proliferative properties were confirmed by accumulation of luteolin-treated cells in sub-G
Language	English
Publishing date	2021-01-07
Publishing country	Greece
Document type	Journal Article
ZDB-ID	2573196-8
ISSN	1792-1082 ; 1792-1074
ISSN (online)	1792-1082
ISSN	1792-1074
DOI	10.3892/ol.2021.12452
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Article ; Online: Interactions between extracellular signal-regulated kinase 1/2 and P38 MAP kinase pathways in the control of RUNX2 phosphorylation and transcriptional activity.

Ge, Chunxi / Yang, Qian / Zhao, Guisheng / Yu, Hong / Kirkwood, Keith L / Franceschi, Renny T

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

2021 Volume 36, Issue 10, Page(s) 2096–2097

Language	English
Publishing date	2021-05-18
Publishing country	United States
Document type	Published Erratum
ZDB-ID	632783-7
ISSN	1523-4681 ; 0884-0431
ISSN (online)	1523-4681
ISSN	0884-0431
DOI	10.1002/jbmr.4300
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Article ; Online: MAP kinase pathways.

Morrison, Deborah K

Cold Spring Harbor perspectives in biology

2012 Volume 4, Issue 11

MeSH term(s)	Cell Death/physiology ; Cell Differentiation/physiology ; Cell Proliferation ; Enzyme Activation/physiology ; Mitogen-Activated Protein Kinases/metabolism ; Mitogen-Activated Protein Kinases/physiology ; Models, Biological ; Phosphorylation ; Signal Transduction/physiology
Chemical Substances	Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2012-11-01
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1943-0264
ISSN (online)	1943-0264
DOI	10.1101/cshperspect.a011254
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Article ; Online: Deficiency in Retinal TGFβ Signaling Aggravates Neurodegeneration by Modulating Pro-Apoptotic and MAP Kinase Pathways

Christina B. Bielmeier / Sabrina I. Schmitt / Nikolai Kleefeldt / Stefaniya K. Boneva / Anja Schlecht / Mario Vallon / Ernst R. Tamm / Jost Hillenkamp / Süleyman Ergün / Andreas Neueder / Barbara M. Braunger

International Journal of Molecular Sciences, Vol 23, Iss 2626, p

2022 Volume 2626

Abstract: ... of the MAP kinase pathway. Therefore, TGFβ signaling in retinal neurons and Müller cells exhibits ...

Abstract	Transforming growth factor β (TGFβ) signaling has manifold functions such as regulation of cell growth, differentiation, migration, and apoptosis. Moreover, there is increasing evidence that it also acts in a neuroprotective manner. We recently showed that TGFβ receptor type 2 ( Tgfbr2 ) is upregulated in retinal neurons and Müller cells during retinal degeneration. In this study we investigated if this upregulation of TGFβ signaling would have functional consequences in protecting retinal neurons. To this end, we analyzed the impact of TGFβ signaling on photoreceptor viability using mice with cell type-specific deletion of Tgfbr2 in retinal neurons and Müller cells ( Tgfbr2 ΔOC ) in combination with a genetic model of photoreceptor degeneration (VPP). We examined retinal morphology and the degree of photoreceptor degeneration, as well as alterations of the retinal transcriptome. In summary, retinal morphology was not altered due to TGFβ signaling deficiency. In contrast, VPP-induced photoreceptor degeneration was drastically exacerbated in double mutant mice ( Tgfbr2 ΔOC VPP) by induction of pro-apoptotic genes and dysregulation of the MAP kinase pathway. Therefore, TGFβ signaling in retinal neurons and Müller cells exhibits a neuroprotective effect and might pose promising therapeutic options to attenuate photoreceptor degeneration in humans.
Keywords	TGFβ signaling ; retina ; retinitis pigmentosa ; neuro-/photoreceptor degeneration ; MAP kinase pathway ; ferroptosis ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	572
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: The Specific IKKε/TBK1 Inhibitor Amlexanox Suppresses Human Melanoma by the Inhibition of Autophagy, NF-κB and MAP Kinase Pathways.

Möller, Moritz / Wasel, Julia / Schmetzer, Julia / Weiß, Ulrike / Meissner, Markus / Schiffmann, Susanne / Weigert, Andreas / Möser, Christine V / Niederberger, Ellen

International journal of molecular sciences

2020 Volume 21, Issue 13

Abstract: ... progression potentially by the inhibition of autophagy as well as NF-кB and MAP kinase pathways and ... ERK pathways might be involved in kinase-mediated effects. In an in vivo xenograft model in nude mice ... Inhibitor-kappaB kinase epsilon (IKKε) and TANK-binding kinase 1 (TBK1) are non-canonical IκB ...

Abstract	Inhibitor-kappaB kinase epsilon (IKKε) and TANK-binding kinase 1 (TBK1) are non-canonical IκB kinases, both described as contributors to tumor growth and metastasis in different cancer types. Several hints indicate that they are also involved in the pathogenesis of melanoma; however, the impact of their inhibition as a potential therapeutic measure in this "difficult-to-treat" cancer type has not been investigated so far. We assessed IKKε and TBK1 expression in human malignant melanoma cells, primary tumors and the metastasis of melanoma patients. Both kinases were expressed in the primary tumor and in metastasis and showed a significant overexpression in tumor cells in comparison to melanocytes. The pharmacological inhibition of IKKε/TBK1 by the approved drug amlexanox reduced cell proliferation, migration and invasion. Amlexanox did not affect the cell cycle progression nor apoptosis induction but significantly suppressed autophagy in melanoma cells. The analysis of potential functional downstream targets revealed that NF-кB and ERK pathways might be involved in kinase-mediated effects. In an in vivo xenograft model in nude mice, amlexanox treatment significantly reduced tumor growth. In conclusion, amlexanox was able to suppress tumor progression potentially by the inhibition of autophagy as well as NF-кB and MAP kinase pathways and might therefore constitute a promising candidate for melanoma therapy.
MeSH term(s)	Aminopyridines/metabolism ; Aminopyridines/pharmacology ; Animals ; Autophagy/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Humans ; I-kappa B Kinase/antagonists & inhibitors ; I-kappa B Kinase/metabolism ; Melanoma/drug therapy ; Melanoma/metabolism ; Mice ; Mice, Nude ; Mitogen-Activated Protein Kinases/metabolism ; NF-kappa B/metabolism ; Protein Kinase Inhibitors/pharmacology ; Protein Serine-Threonine Kinases/antagonists & inhibitors ; Protein Serine-Threonine Kinases/metabolism ; Xenograft Model Antitumor Assays
Chemical Substances	Aminopyridines ; NF-kappa B ; Protein Kinase Inhibitors ; amlexanox (BRL1C2459K) ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; TBK1 protein, human (EC 2.7.11.1) ; I-kappa B Kinase (EC 2.7.11.10) ; IKBKE protein, human (EC 2.7.11.10) ; Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2020-07-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21134721
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