Search results for " Protein kinases"
showing 10 items of 342 documents
Midregion PTHrP regulates Rip1 and caspase expression in MDA-MB231 breast cancer cells.
2007
It was previously reported that the midregion PTHrP domain (38-94)-amide restrains growth and invasion "in vitro", causes striking toxicity and accelerates death of some breast cancer cell lines, the most responsive being MDA-MB231 whose tumorigenesis was also attenuated "in vivo". In addition, we have demonstrated that midregion PTHrP is imported in the nucleoplasm of cultured MDA-MB231 cells, and that "in vitro" it can bind chromatin of metaphase spread preparations and also an isolated 20-mer oligonucleotide, thereby appearing endowed with a putative transcription factor-like DNA-binding ability. Here, we examined whether PTHrP (38-94)-amide was able to modulate the expression of genes e…
The role of oxidative stress in apoptosis induced by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in human colon adenocarcinoma …
2008
Histone deacetylase inhibitors (HDACIs) activate genes that promote cell cycle arrest and apoptosis in a number of tumor cells. This study showed that suberoylanilide hydroxamic acid (SAHA), a potent and commonly used HDACI, induced apoptosis in human colon adenocarcinoma HT-29 cells in a time- and dose-dependent manner. This effect was accompanied by the induction of oxidative stress, dissipation of mitochondrial transmembrane potential and activation of executioner caspases. Moreover, SAHA increased the levels of phosphorylated active forms of p38 and JNK. The addition of either the antioxidant N-acetylcysteine or the specific inhibitor of NADPH oxidase diphenylene iodonium chloride reduc…
Apoptosis induced in HepG2 cells by the synthetic cannabinoid WIN: involvement of the transcription factor PPARgamma.
2008
It has recently been shown that cannabinoids induce growth inhibition and apoptosis in different tumour cell lines. In the current study, the effects of WIN 55,212-2 (WIN), a synthetic and potent cannabinoid receptor agonist, are investigated in hepatoma HepG2 cells and a possible signal transduction pathway is proposed. In these cells, WIN induces a clear apoptotic effect which was accompanied by up-regulation of the death-signalling factors Bax, Bcl-X(S), t-Bid and down-regulation of the survival factors survivin, phospho-AKT, Hsp72 and Bcl-2. Moreover, WIN-induced apoptosis is associated with JNK/p38 MAPK pathway activation and mitochondrial depolarisation demonstrated by a cytofluorimet…
Transcriptional and post-transcriptional regulation of iNOS expression in human chondrocytes
2009
Chondrocytes are important for the development and maintenance of articular cartilage. However, both in osteoarthritis (OA) and rheumatoid arthritis (RA) chondrocytes are involved in the process of cartilage degradation and synthesize important immunomodulatory mediators, including nitric oxide (NO) generated by the inducible NO synthase (iNOS). To uncover the role of iNOS in the pathomechanisms of OA and RA, we analyzed the regulation of iNOS expression using immortalized human chondrocytes as a reproducible model. In C-28/I2 chondrocytes, iNOS expression was associated with the expression of the chondrocyte phenotype. Peak induction by a cytokine cocktail occurred between 6 and 8h and dec…
Cigarette Smoke Extract Induces p38 MAPK-Initiated, Fas-Mediated Eryptosis
2022
Eryptosis is a physiological mechanism for the clearance of senescent or damaged erythrocytes by phagocytes. Excessive eryptosis is stimulated under several pathologies and associated with endothelial injury and thrombosis. Cigarette smoke (CS) is an established risk factor for vascular diseases and cigarette smokers have high-levels of eryptotic erythrocytes. This study, for the first time, investigates the mechanism by which CS damages red blood cells (RBCs). CS extract (CSE) from commercial cigarettes was prepared and standardized for nicotine content. Cytofluorimetric analysis demonstrated that treatment of human RBCs with CSE caused dose-dependent, phosphatidylserine externalization an…
Dynamics of Ca2+ and guanosine 5'-[gamma-thio]triphosphate action on insulin secretion from alpha-toxin-permeabilized HIT-T15 cells.
1994
The time course of Ca2+ and GTP-analogue effects on insulin secretion was investigated in HIT-T15 cells permeabilized with Staphylococcus alpha-toxin. These cells responded to Ca2+ in the range 0.1-10 microM and could be used in a dynamic perifusion system because of the minimal run-down of the secretory response. High Ca2+ (10 microM) elicited a monophasic ATP-dependent stimulation of insulin secretion that reached a peak within 5 min (approximately 20-fold increase) and rapidly decreased during the subsequent 15 min to a plateau remaining above basal rates (0.1 microM Ca2+). The decrease in Ca(2+)-induced insulin secretion with time could not be attributed to decreased capacity to respond…
Cisplatin sensitivity is related to late DNA damage processing and checkpoint control rather than to the early DNA damage response
2008
The present study aimed at elucidating mechanisms dictating cell death triggered by cisplatin-induced DNA damage. We show that CL-V5B hamster mutant cells, a derivative of V79B, are hypersensitive to cisplatin-induced apoptotic death. CL-V5B cells are characterized by attenuated cisplatin-induced early (2-6 h) stress response, such as phosphorylation of stress-activated protein kinases (SAPK/JNK), ATM and Rad3-related (ATR) protein kinase, histone H2AX and checkpoint kinase-1 (Chk-1). Human FANCC cells also showed a reduced phosphorylation of H2AX and SAPK/JNK at early time point after cisplatin treatment. This was not the case for BRCA2-defective VC-8 hamster cells, indicating that the FA …
Distinct Signaling Cascades of TREM-1, TLR and NLR in Neutrophils and Monocytic Cells
2013
Triggering receptor expressed on myeloid cells 1 (TREM-1) is an important mediator of innate inflammatory responses in microbial infections and sepsis. TREM-1 ligation on neutrophils (PMN) or monocytes results in the production of proinflammatory cytokines. Engagement of TREM-1 induces the activation of MAP kinases as well as rapid Ca<sup>2+</sup> mobilization. However, a detailed understanding of TREM-1 signaling pathways is currently lacking. We evaluated the TREM-1 signaling hierarchy in monocytic cells and found that the acute myeloid leukemia cell line MUTZ-3 expresses TREM-1 in a natural and functional manner. We compared essential signaling molecules of the TREM-1, TLR an…
Interplay of oxidants and antioxidants during exercise: Implications for muscle health
2010
Muscle contraction results in generation of reactive oxygen and nitrogen species (RONS) at a rate determined by the intensity, frequency, and duration of the exercise protocols. Strenuous exercise causes oxidation of protein, lipid, and DNA, release of cytosolic enzymes, and other signs of cell damage; however, only exhaustive exercise is detrimental. Indeed, the regulation of vascular tone, the excitation-contraction coupling, growth, and differentiation in skeletal muscle, are governed in part by RONS. This is accomplished by RONS interaction with redox-sensitive transcription factors, leading to increased gene expression of antioxidant enzymes, cytoprotective proteins, and other enzymes …
Role of cAMP in mediating AHR signaling.
2009
Regulation of the nuclear import of many transcription factors represents a step in gene regulation which is crucial for a number of cellular processes. The aryl hydrocarbon receptor (AHR), a basic helix-loop-helix protein of the PAS (PER-ARNT-SIM) family of transcriptional regulators is a cytosol-associated and ligand-activated receptor. The environmental toxin dioxin binds with high affinity to AHR rendering it nuclear and leading to the activation of AHR sensitive genes. However, the fact, that the AHR mediates a large variety of physiological events without the involvement of any known exogenous ligand, including liver and vascular system development, maturation of the immune system, re…