Abstract:
:The signal transducer and activator of transcription 3 (STAT3) transduces stress signals from the plasma membrane to the nucleus but has recently also been identified in mitochondria. Inhibition of cardiomyocyte mitochondrial STAT3 with the STAT3-specific inhibitor Stattic decreases ADP-stimulated respiration and enhances calcium-induced mitochondrial permeability transition pore (MPTP) opening. The aim of the present study was to analyze whether or not these effects of STAT3 inhibition by Stattic are mediated by the formation of reactive oxygen species (ROS). The H2O2 formation from isolated rat left ventricular mitochondria was measured continuously in the presence of the complex 1 substrates glutamate and malate using the H2O2 indicator Amplex UltraRed. Stattic dose-dependently increased mitochondrial ROS formation (slope of Amplex UltraRed fluorescence/time; DMSO: 0.39±0.01; 1 µM Stattic: 0.40±0.03; 10 µM Stattic: 0.71±0.04; 25 µM Stattic: 1.43±0.05; 50 µM Stattic: 3.53±0.23; 100 µM Stattic: 9.23±0.69, n=5 mitochondrial preparations, p<0.05 for 10-100 µM Stattic). The increase in the ROS signal by 100 µM Stattic was abolished in the presence of the ROS scavenger N-acetylcysteine (Nac, 0.46±0.02, n=7, p<0.05). Mitochondria treated with 100 µM Stattic produced less ATP than control mitochondria (86±3 arbitrary units (a.u.) vs. 128±7 a.u., n=9, p<0.05). Again, in the presence of Nac ATP production was similar between Stattic-treated and control mitochondria (142±4 a.u. vs. 147±12 a.u., n=5, p=ns). MPTP opening was induced by lower amounts of calcium in Stattic-treated than in control mitochondria (in nmol CaCl2/mg protein, Stattic: 507±57, n=7; control: 857±70, n=7, p<0.05). There was no difference in calcium-induced MPTP opening between Stattic-treated (833±57, n=6) and control mitochondria (921±75, n=7, p=ns) in the presence of Nac. Taken together, our data show that inhibition of mitochondrial STAT3 by Stattic impacts on mitochondrial ATP production and MPTP opening through enhanced ROS formation.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Boengler K,Ungefug E,Heusch G,Schulz Rdoi
10.2174/138161281939131127115940subject
Has Abstractpub_date
2013-01-01 00:00:00pages
6890-5issue
39eissn
1381-6128issn
1873-4286pii
CPD-EPUB-20130410-9journal_volume
19pub_type
杂志文章abstract::The rapid advancement of computer architectures and development of mathematical algorithms offer a unique opportunity to leverage the simulation of macromolecular systems at physiologically relevant timescales. Herein, we discuss the impact of diverse structure-based and ligand-based molecular modeling techniques in d...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190304123545
更新日期:2019-01-01 00:00:00
abstract::Cellular uptake of therapeutic oligonucleotides and subsequent intracellular trafficking to their target sites represents the major technical hurdle for the biological effectiveness of these potential drugs. Accordingly, laboratories worldwide focus on the development of suitable delivery systems. Among the different ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208786898806
更新日期:2008-01-01 00:00:00
abstract::The incidence of diabetes has increased globally in recent years and figures of diabetic patients were estimated to rise up to 642 million by 2040. The disorder is accompanied with various complications if not managed at the early stages, and interlinked high mortality rate and morbidity with time. Different classes o...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190717104547
更新日期:2019-01-01 00:00:00
abstract::The heart is a sophisticated endocrine gland synthesizing a family of peptide hormones by three different genes. These cardiac hormones are stored as 3 prohormones, i.e. atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) prohormones. Within the ANP prohormones are 4 ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210790963887
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Hepatocellular carcinoma (HCC) has high mortality partly due to acquiring drug resistance during chemotherapy treatment. Therefore, it is necessary to explore the underlying mechanism of drug resistance. METHODS:We used 2-DE and MALDI-TOF-MS analysis to explore the possible molecular insight into 5-FU resis...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161282001140113125143
更新日期:2014-01-01 00:00:00
abstract::Pro-rich antimicrobial peptides are a group of linear peptides of innate immunity isolated from mammals and invertebrates, and characterised by a high content of proline residues (up to 50%). Members of this group are predominantly active against Gram-negative bacterial species which they kill by a non-lytic mechanism...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023395394
更新日期:2002-01-01 00:00:00
abstract::We conducted a systematic review on resting state cerebral blood flow activities found in first-episode psychosis (FEP) and during acute effects of cannabinoids and opioids, mental states that can be profoundly different from normal functioning. The main goal was to identify connections of cerebral blood flow measure ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212802884717
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Cyclodextrins (CDs), as one type of the novel pharmaceutical excipients, have been widely used in drug delivery and pharmaceutical industry. Over the past decades, a large amount of molecular modeling studies in CDs were reported for profound understanding of structural, dynamic and energetic features of CDs...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666161208142617
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:The failing heart is characterized by a depleted metabolic energy reserve and the upregulation of several molecular mechanisms leading to cardiac hypertrophy, inflammation, fibrosis, angiogenesis, and apoptosis. Dietary or non-dietary supplementation of vitamins could potentially benefit energy balance. OBJ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170321094711
更新日期:2017-01-01 00:00:00
abstract::Biochemical biomarkers are important candidates for the diagnosis and prognosis of neurological diseases of autoimmune etiology, since they may reflect the presence, nature and intensity of certain immune responses caused by both genetic and environmental processes. Different body fluids such as cerebrospinal fluid (C...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212802502143
更新日期:2012-01-01 00:00:00
abstract::Sex-dependent differences are frequently observed in the biological and behavioural effects of substances of abuse, including cannabis. We recently demonstrated a modulating effect of sex and oestrous cycle on cannabinoid-taking and seeking behaviours. Here, we investigated the influence of sex and oestrogen in the re...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990430
更新日期:2014-01-01 00:00:00
abstract::Aberrant expression of chemokines and their receptors play causative roles in the pathophysiology of numerous autoimmune and inflammatory disease processes. Moreover, an integral step in HIV infection involves binding to chemokine receptors, and hence chemokines are intimately linked to HIV-related diseases. Therefore...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023393233
更新日期:2002-01-01 00:00:00
abstract::Lysine acetylation plays an essential role in metabolism. Five individual studies have identified that a large number of cellular proteins are potentially acetylated. Notably, almost every enzyme involved in central metabolic pathways such as glycolysis, the TCA cycle, fat acid metabolism, urea cycle and glycogen meta...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990487
更新日期:2014-01-01 00:00:00
abstract::Cumulative scientific evidence gathered over the past ten years has confirmed the role of platelet GP IIb/IIIa inhibitors in reducing ischemic complications of patients undergoing percutaneous coronary intervention (PCI). Recently, mortality data available on more than 20,000 patients enrolled in randomized clinical t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043453306
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:R. Schofield (1978) proposed a hypothesis of hematopoietic stem cells (HSCs) niche (specialized cell microenvironment). An existence of osteoblastic and vascular niches for HSCs has been postulated since 2003. At the same time, the discussion about the existence and functioning of niche for multipotent mesen...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180829154119
更新日期:2018-01-01 00:00:00
abstract::α-Synuclein aggregation is centrally implicated in Parkinson's disease (PD). It involves multi-step nucleated polymerization process via the formation of dimers, soluble toxic oligomers and insoluble fibrils. In the present study, we synthesized a novel compound viz., Curcumin-glucoside (Curc-gluc), a modified form of...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161212798919093
更新日期:2012-01-01 00:00:00
abstract::We illustrate the use of quantitative proteomics, namely isotope-coded affinity tag labelling and tandem mass spectrometry, to assess the targets and effects of the blockade of matrix metalloproteinases by an inhibitor drug in a breast cancer cell culture system. Treatment of MT1-MMP-transfected MDA-MB-231 cells with ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207779313524
更新日期:2007-01-01 00:00:00
abstract::Neuregulin1 proteins (NRG1s) are epidermal growth factor (EGF) family members which are ligands for the ErbB receptor tyrosine kinases (RTKs). A decade of research has revealed that the NRG1-ErbB signaling is essential for the cardiac development and pivotal for maintaining the physiological function of the adult hear...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211796391010
更新日期:2011-01-01 00:00:00
abstract::Propofol (2, 6-diisopropylphenol) is a potent intravenous hypnotic agent which is widely used for the induction and maintenance of anesthesia and for sedation in the intensive care unit. Propofol is an oil at room temperature and insoluble in aqueous solution. Present formulations consists of 1% or 2% (w/v) propofol, ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043382846
更新日期:2004-01-01 00:00:00
abstract::Oral epithelium is a stratified squamous epithelium that functions as the barrier between the outside environment and the host. In the oral cavity, epithelial tissues are constantly exposed to a variety of bacteria, but most individuals maintain healthy homeostasis. Epithelial cells contribute to the innate host respo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207782110435
更新日期:2007-01-01 00:00:00
abstract::This review will focus on the construction, refinement, and validation of G Protein-coupled receptor models for the purpose of structure-based virtual screening. Practical tips and tricks derived from concrete modeling and virtual screening exercises to overcome the problems and pitfalls associated with the different ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209789824786
更新日期:2009-01-01 00:00:00
abstract::Nucleosides constitute an extensive group of natural and chemically modified compounds that display a wide range of structures and activities. Different biocatalysts have been developed for their preparation, but the choice of commercially available enzymes is limited. Therefore, the search of new biocatalysts is part...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612823666171011101133
更新日期:2017-10-11 00:00:00
abstract:BACKGROUND:Cardiac resynchronization therapy (CRT) is a valuable intracardiac device--based treatment option for a subgroup of patients with advanced heart failure (HF) and QRS prolongation. However, still a significant proportion of patients do not benefit from CRT implantation, labeled as non-responders. OBJECTIVES:...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612825666190621155718
更新日期:2019-01-01 00:00:00
abstract:BACKGROUNDS:Targeted therapy is the foundation of personalized medicine in cancer, which is often understood as the right patient using the right drug. Thinking from the viewpoint of determinants during personalized drug treatment, the genetics, epigenetics and metagenomics would provide individual-specific biological ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666181106102111
更新日期:2018-01-01 00:00:00
abstract::microRNAs (miRNAs) comprise a recently discovered class of non-coding RNAs with regulatory functions in post-transcriptional gene expression control. Many miRNAs are located in genomic regions that are frequently deleted in cancer, or are subject to epigenetic and transcriptional deregulation in cancer cells. The miRN...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161213804805649
更新日期:2013-01-01 00:00:00
abstract::Cerebral ischemia is one of the major causes of disability worldwide. In cerebral ischemic stroke, occlusion of a major cerebral artery by an embolus or local thrombosis can result in transient or permanent reduction of cerebral blood flow to a portion of the brain, resulting in deprivation of glucose and oxygen. Sinc...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990465
更新日期:2014-01-01 00:00:00
abstract::Following injury, as part of the wound-healing process, cell proliferation occurs mostly to replace damaged cells and to reconstitute the tissue back to normal condition/function. In the spinal cord some of the dividing cells following injury interfere with the repair processes. This interference occurs at the later s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612053507477
更新日期:2005-01-01 00:00:00
abstract::Recent progresses in the development of fluorescent technologies become a reliable device for drug discovery research. The fluorescence tools offer attractive options for an opportunity to visualize the effects of drug candidates in the cells. The fluorescent tools, such as fluorescent protein, are regularly used in a...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209789207006
更新日期:2009-01-01 00:00:00
abstract::Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle and RNA polymerase II transcription. Several pharmacological CDK inhibitors (PCIs) are currently in clinical trials as potential cancer therapeutics since CDK hyperactivation is detected in the majority of neoplasias. Within the last few years, the a...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777442083
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Origanum vulgare is used in Armenian cuisine as well as in folk medicine. The aim of this investigation was to determine the peculiarities of the chemical composition of Armenian flora's oregano essential oil (EO) and ethanol extract (EE) and to characterize mainly antioxidant and antibacterial properties in...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612825666190702095612
更新日期:2019-01-01 00:00:00