Search results for "Transduction"
showing 10 items of 2149 documents
Increased Connexin 43 Expression as a Potential Mediator of the Neuroprotective Activity of the Corticotropin-Releasing Hormone
2009
CRH is a major central stress mediator, but also a potent neuroprotective effector. The mechanisms by which CRH mediates its neuroprotective actions are largely unknown. Here, we describe that the gap junction molecule connexin43 (Cx43) mediates neuroprotective effects of CRH toward experimentally induced oxidative stress. An enhanced gap junction communication has been reported to contribute to neuroprotection after neurotoxic insults. We show that CRH treatment up-regulates Cx43 expression and gap junctional communication in a CRH receptor-dependent manner in IMR32 neuroblastoma cells, primary astrocytes, and organotypic hippocampal slice cultures. MAPKs and protein kinase A-cAMP response…
Endothelial Bmx tyrosine kinase activity is essential for myocardial hypertrophy and remodeling
2015
Cardiac hypertrophy accompanies many forms of heart disease, including ischemic disease, hypertension, heart failure, and valvular disease, and it is a strong predictor of increased cardiovascular morbidity and mortality. Deletion of bone marrow kinase in chromosome X (Bmx), an arterial nonreceptor tyrosine kinase, has been shown to inhibit cardiac hypertrophy in mice. This finding raised the possibility of therapeutic use of Bmx tyrosine kinase inhibitors, which we have addressed here by analyzing cardiac hypertrophy in gene-targeted mice deficient in Bmx tyrosine kinase activity. We found that angiotensin II (Ang II)-induced cardiac hypertrophy is significantly reduced in mice deficient i…
Role of insulin-like growth factors in autocrine growth of human retinoblastoma Y79 cells.
1996
In this study, we have demonstrated that human retinoblastoma Y79 cells produce insulin-like growth factors (IGFs) type I and type II and release them into the medium. We have also ascertained, by means of competitive studies and cross-linking procedure, that Y79 cells contain the type-I IGF receptor (IGF-IR). Furthermore, surface-bound IGF-I is internalised by the receptor, then degraded to amino acids. Insulin, IGF-I and IGF-II caused down-regulation of IGF-IR; the effect is concentration and time dependant. Scatchard analysis demonstrated that incubation with insulin markedly decreased the binding capacity measured for IGF-I while the apparent Kd value calculated for IGF-I binding was no…
Smoking and Neuropsychiatric Disease-Associations and Underlying Mechanisms.
2021
Despite extensive efforts to combat cigarette smoking/tobacco use, it still remains a leading cause of global morbidity and mortality, killing more than eight million people each year. While tobacco smoking is a major risk factor for non-communicable diseases related to the four main groups—cardiovascular disease, cancer, chronic lung disease, and diabetes—its impact on neuropsychiatric risk is rather elusive. The aim of this review article is to emphasize the importance of smoking as a potential risk factor for neuropsychiatric disease and to identify central pathophysiological mechanisms that may contribute to this relationship. There is strong evidence from epidemiological and experiment…
INHIBITION OF CELLULAR GROWTH AND STEROID 11β-HYDROXYLATION INRAS-TRANSFORMED ADRENOCORTICAL CELLS BY THE FUNGAL TOXINS BETICOLINS
1996
Abstract The proliferation of GM16 and 4CDTras-transformed newborn rat adrenocortical (RTAC) cells and Y1 mouse adrenal tumor cells was inhibited by beticolins, the fungal toxins extracted fromCercospora beticola, at submicromolar concentrations in a dose-dependent manner. Inhibitory concentrations for half the maximum inhibition were 150, 75 and 25 n M for beticolin-1 and 230, 150 and 50 n M for beticolin-2 in GM16, 4CDT and Y1 cells respectively. Beticolins strongly inhibited the production of 11β-hydroxysteroids on the second and third days of treatment in a dose-dependent manner between 0.1 and 1 μ M . Beticolins were shown by confocal microscopy to be localized in cytoplasmic organelle…
Inhibition of the NF-κB Signaling Pathway Mediates the Anti-inflammatory Effects of Petrosaspongiolide M
2003
Petrosaspongiolide M (PT) is a potent secretory phospholipase A(2) inhibitor and anti-inflammatory agent. This marine metabolite reduced the production of nitrite, prostaglandin E(2), and tumor necrosis factor-alpha in the mouse air pouch injected with zymosan. These effects were also observed in mouse peritoneal macrophages stimulated with zymosan. Inhibition of these inflammatory mediators was related to reductions in inducible nitric oxide synthase, cyclo-oxygenase-2, and tumor necrosis factor-alpha expression. Since nuclear factor-kappaB (NF-kappaB) appears to play a central role in the transcriptional regulation of these proteins by macrophages, we investigated the effects of PT on thi…
Novel Combination of Sorafenib and Celecoxib Provides Synergistic Anti-Proliferative and Pro-Apoptotic Effects in Human Liver Cancer Cells
2013
Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, recently received FDA approval for the treatment of advanced HCC. However, although sorafenib is well tolerated, concern for its safety has been expressed. Celecoxib (Celebrex®) is a selective cyclooxygenase-2 (COX-2) inhibitor which exhibits antitumor effects in human HCC cells. The present study examined the interaction between celecoxib and sorafenib in two human liver tumor cell lines HepG2 and Huh7. Our data showed that each inhibitor alone reduced cell growth and the combination of celecoxib with sorafenib synergistically inhibited cell growth an…
The Potential Use of Resveratrol for Cancer Prevention.
2019
In addition to the traditional treatments of cancer and cancer prevention, the use of natural compounds, especially those found in food, should be considered. To clarify if resveratrol has the potential for cancer prevention and the possibility of use in therapy, the following must be taken into account: data from epidemiology, clinical protocol (case and control), preclinical studies (lab animals), use of established cell lines as models of cancer cells, test tube assays (enzymes activities), and requirements of nanotechnologies in order to discover new drugs to fight cancer. From this perspective and future expected advances, more information is needed such as improved efficacy, methods o…
Bortezomib Induces Anti–Multiple Myeloma Immune Response Mediated by cGAS/STING Pathway Activation
2021
Abstract The proteasome inhibitor bortezomib induces apoptosis in multiple myeloma cells and has transformed patient outcome. Using in vitro as well as in vivo immunodeficient and immunocompetent murine multiple myeloma models, we here show that bortezomib also triggers immunogenic cell death (ICD), characterized by exposure of calreticulin on dying multiple myeloma cells, phagocytosis of tumor cells by dendritic cells, and induction of multiple myeloma–specific immunity. We identify a bortezomib-triggered specific ICD gene signature associated with better outcome in two independent cohorts of patients with multiple myeloma. Importantly, bortezomib stimulates multiple myeloma cell immunogen…
Dendritic Cell-Specific Deletion of β-Catenin Results in Fewer Regulatory T-Cells without Exacerbating Autoimmune Collagen-Induced Arthritis.
2015
Dendritic cells (DCs) are professional antigen presenting cells that have the dual ability to stimulate immunity and maintain tolerance. However, the signalling pathways mediating tolerogenic DC function in vivo remain largely unknown. The beta-catenin pathway has been suggested to promote a regulatory DC phenotype. The aim of this study was to unravel the role of beta-catenin signalling to control DC function in the autoimmune collagen-induced arthritis model (CIA). Deletion of beta-catenin specifically in DCs was achieved by crossing conditional knockout mice with a CD11c-Cre transgenic mouse line. Bone marrow-derived DCs (BMDCs) were generated and used to study the maturation profile of …