Biochimica et biophysica acta
-
Biochim. Biophys. Acta · Jan 2014
Prophylactic systemic P2X7 receptor blockade prevents experimental colitis.
The P2X7 receptor (P2X7-R) is a non-selective adenosine triphosphate-gated cation channel present in epithelial and immune cells, and involved in inflammatory response. Extracellular nucleotides released in conditions of cell stress or inflammation may function as a danger signal alerting the immune system from inflammation. We investigated the therapeutic action of P2X7-R blockade in a model of inflammatory bowel disease. ⋯ Prophylactic systemic P2X7-R blockade is effective in the prevention of experimental colitis, probably due to a systemic anti-inflammatory action, interfering with a stress-inflammation amplification loop mediated by P2X7-R.
-
Biochim. Biophys. Acta · Jan 2014
Randomized Controlled TrialResveratrol enhances TNF-α production in human monocytes upon bacterial stimulation.
Resveratrol is a key component of red wine that has been reported to have anti-carcinogenic and anti-aging properties. Additional studies conducted in vitro and in animal models suggested anti-inflammatory properties. However, data from primary human immune cells and in vivo studies are limited. ⋯ By administering resveratrol to healthy humans and utilizing primary immune cells we were able to detect TNF-α enhancing properties of the agent. In parallel, we found enhanced alternative NF-κB activation. We report on a novel pro-inflammatory property of resveratrol which has to be considered in concepts of its biologic activity.
-
Biochim. Biophys. Acta · Jan 2014
ReviewCreate and preserve: proteostasis in development and aging is governed by Cdc48/p97/VCP.
The AAA-ATPase Cdc48 (also called p97 or VCP) acts as a key regulator in proteolytic pathways, coordinating recruitment and targeting of substrate proteins to the 26S proteasome or lysosomal degradation. However, in contrast to the well-known function in ubiquitin-dependent cellular processes, the physiological relevance of Cdc48 in organismic development and maintenance of protein homeostasis is less understood. Therefore, studies on multicellular model organisms help to decipher how Cdc48-dependent proteolysis is regulated in time and space to meet developmental requirements. ⋯ This article is part of a Special Issue entitled: Ubiquitin-Proteasome System. Guest Editors: Thomas Sommer and Dieter H. Wolf.
-
Heart failure (HF) biomarkers have dramatically impacted the way HF patients are evaluated and managed. B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are the gold standard biomarkers in determining the diagnosis and prognosis of HF, and studies on natriuretic peptide-guided HF management look promising. ⋯ Novel biomarkers, such as mid-regional pro atrial natriuretic peptide (MR-proANP), mid-regional pro adrenomedullin (MR-proADM), highly sensitive troponins, soluble ST2 (sST2), growth differentiation factor (GDF)-15 and Galectin-3, show potential in determining prognosis beyond the established natriuretic peptides, but their role in the clinical care of the patient is still partially defined and more studies are needed. This article is part of a Special Issue entitled: Heart failure pathogenesis and emerging diagnostic and therapeutic interventions.
-
Biochim. Biophys. Acta · Dec 2013
ReviewEndothelial dysfunction - a major mediator of diabetic vascular disease.
The vascular endothelium is a multifunctional organ and is critically involved in modulating vascular tone and structure. Endothelial cells produce a wide range of factors that also regulate cellular adhesion, thromboresistance, smooth muscle cell proliferation, and vessel wall inflammation. Thus, endothelial function is important for the homeostasis of the body and its dysfunction is associated with several pathophysiological conditions, including atherosclerosis, hypertension and diabetes. ⋯ This review will focus on the mechanisms and therapeutics that specifically target endothelial dysfunction in the context of a diabetic setting. Mechanisms including altered glucose metabolism, impaired insulin signaling, low-grade inflammatory state, and increased reactive oxygen species generation will be discussed. The importance of developing new pharmacological approaches that upregulate endothelium-derived nitric oxide synthesis and target key vascular ROS-producing enzymes will be highlighted and new strategies that might prove clinically relevant in preventing the development and/or retarding the progression of diabetes associated vascular complications.