Search results for "NF-"
showing 10 items of 461 documents
Antitumor effects of curcumin and structurally β-diketone modified analogs on multidrug resistant cancer cells
2007
Abstract Using concepts of bioisostery a series of curcumin analogs were synthesized: the diketonic system of the compound was elaborated into enaminones, oximes, and the isoxazole heterocycle. The cell growth inhibitory and apoptosis inducing effects of the new analogs were evaluated by in vitro assays in the hepatocellular carcinoma HA22T/VGH cells, as well as in the MCF-7 breast cancer cell line and in its multidrug resistant (MDR) variant MCF-7R. Increased antitumor activity on all cell lines was found with the isoxazole analog and especially with the benzyl oxime derivative; in the HA22T/VGH cell model, the latter compound inhibited constitutive NF-κB activation.
Exercise and antioxidant supplements in the elderly
2013
Abstract Both exercise and aging increase reactive oxygen species (ROS), which can result in damage to cells. Aging is the result of damage caused by ROS to the mitochondrial genome in post mitotic cells and numerous studies have demonstrated an increase in ROS or their byproducts with exercise. ROS can cause oxidative stress as they overwhelm the antioxidant cellular defenses. Therefore interventions aimed at limiting or inhibiting ROS production, such as supplementation with antioxidant vitamins, should be able to reduce fatigue during muscle contraction and the rate of formation of aging changes with a consequent reduction of the aging rate and disease pathogenesis. However, it has been …
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 …
IkappaB kinase 2 determines oligodendrocyte loss by non-cell-autonomous activation of NF-kappaB in the central nervous system
2011
The IκB kinase complex induces nuclear factor kappa B activation and has recently been recognized as a key player of autoimmunity in the central nervous system. Notably, IκB kinase/nuclear factor kappa B signalling regulates peripheral myelin formation by Schwann cells, however, its role in myelin formation in the central nervous system during health and disease is largely unknown. Surprisingly, we found that brain-specific IκB kinase 2 expression is dispensable for proper myelin assembly and repair in the central nervous system, but instead plays a fundamental role for the loss of myelin in the cuprizone model. During toxic demyelination, inhibition of nuclear factor kappa B activation by …
Ras-related GTPase Rhob represses NF-kappaB signaling.
2000
rhoB encoding a Ras-related GTPase is immediate-early inducible by genotoxic treatments, indicating that it is part of the cellular stress response. Here, we investigated the influence of RhoB on signal pathways that are rapidly evoked by genotoxic compounds. The data obtained show that wild-type RhoB neither affects activation of mitogen-activated protein kinases nor AP-1-dependent gene expression. However, RhoB inhibited both basal and genotoxic agent-stimulated activity of the transcription factor nuclear factor kappaB (NF-kappaB). Thus, RhoB attenuated alkylation-induced increase in the DNA binding activity of NF-kappaB and abrogated NF-kappaB-driven gene expression. Furthermore, RhoB i…
Down-regulation of transcription factors AP-1, Sp-1, and NF-kappa B precedes myocyte differentiation.
1996
Terminal differentiation of myocytes involves withdrawal from the cell cycle, induction of myogenin expression, and finally formation of myotubes. To study the factors that regulate the initial phase of muscle differentiation, we analyzed the binding activities of transcription factors AP-1, Sp-1, and NF-kappa B in L6, C2C12, and rhabdomyosarcoma BA-Han-1C cells. Temporal changes in transcription factor binding activities were compared to the activation of myogenin promoter-driven CAT reporter gene and the expression level of myogenin, a master gene of myogenic differentiation. We observed a prominent decrease in the nuclear binding activities of AP-1, Sp-1, and NF-kappa B already 12 to 24 …
Bortezomib induces in HepG2 cells IkappaBalpha degradation mediated by caspase-8.
2006
The present paper demonstrates that the proteasome inhibitor bortezomib, which behaves as an apoptotic agent in hepatoma HepG2 cells, caused in these cells a decrease in IkappaBalpha level and a consequent increase in NF- kappaB activity. The effect already appeared at 4 h of treatment and preceded the onset of apoptosis which was observed at 24 h. Our results demonstrate that bortezomib-induced IkappaBalpha degradation occurred in conjunction with the activation of caspase-8; moreover, the decrease in IkappaBalpha level was prevented in a dose-dependent manner by the addition of z-IETD, a specific inhibitor of caspase-8. Bortezomib caused the same effects in non-tumor Chang liver cells, wh…
Epithelial NEMO links innate immunity to chronic intestinal inflammation
2007
Deregulation of intestinal immune responses seems to have a principal function in the pathogenesis of inflammatory bowel disease(1-4). The gut epithelium is critically involved in the maintenance of intestinal immune homeostasis-acting as a physical barrier separating luminal bacteria and immune cells, and also expressing antimicrobial peptides(3,5,6). However, the molecular mechanisms that control this function of gut epithelial cells are poorly understood. Here we show that the transcription factor NF kappa B, a master regulator of pro-inflammatory responses(7,8), functions in gut epithelial cells to control epithelial integrity and the interaction between the mucosal immune system and gu…
Curcumin effectively inhibits oncogenic NF-κB signaling and restrains stemness features in liver cancer
2015
Background & Aims The cancer stem cells (CSCs) have important therapeutic implications for multi-resistant cancers including hepatocellular carcinoma (HCC). Among the key pathways frequently activated in liver CSCs is NF-κB signaling. Methods We evaluated the CSCs-depleting potential of NF-κB inhibition in liver cancer achieved by the IKK inhibitor curcumin, RNAi and specific peptide SN50. The effects on CSCs were assessed by analysis of side population (SP), sphere formation and tumorigenicity. Molecular changes were determined by RT-qPCR, global gene expression microarray, EMSA, and Western blotting. Results HCC cell lines exposed to curcumin exhibited differential responses to curcumin a…
Role of curcumin in idiopathic pulmonary arterial hypertension treatment: A new therapeutic possibility
2013
The idiopathic pulmonary arterial hypertension is a complex disease that mainly affects pulmonary arterial circulation. This undergoes a remodeling with subsequent reduction of flow in the small pulmonary arteries. Because of this damage an increased vascular resistance gradually develops, and over time it carries out in heart failure. The inflammatory process is a key element in this condition, mediated by various cytokines. The inflammatory signal induces activation of NF-κB, and prompts TGF-β-related signaling pathway. Clinical evolution leads to progressive debilitation, greatly affecting the patient quality of life. The actual therapeutic approaches, are few and expensive, and include …