Inhibition of phosphorylation of TrkB and TrkC and their signal transduction by alpha2-macroglobulin.
Humans; Animals; Mice; Signal Transduction/drug effects/*physiology; Phosphorylation; Mitogen-Activated Protein Kinase 1/metabolism; Antineoplastic Agents/pharmacology; Type C Phospholipases/metabolism; Cell Differentiation/drug effects; Neuroprotective Agents/*metabolism; Neuroblastoma; alpha-Macroglobulins/*pharmacology; *Mitogen-Activated Protein Kinases; 3T3 Cells/chemistry/cytology/enzymology; Brain-Derived Neurotrophic Factor/pharmacology; Calcium-Calmodulin-Dependent Protein Kinases/metabolism; Isoenzymes/metabolism; Mitogen-Activated Protein Kinase 3; Nerve Growth Factors/pharmacology; Neurotrophin 3; Phospholipase C gamma; Receptor Protein-Tyrosine Kinases/*metabolism; Serotonin/metabolism; Tretinoin/pharmacology; Ciliary Neurotrophic Factor; Receptors; Receptor; Tumor Cells; Cultured/chemistry/cytology/enzymology; Nerve Growth Factor/*metabolism; trkC
Monoamine-activated alpha2-macroglobulin (alpha2M) was shown to reduce the dopamine concentration in corpus striatum of adult rat brains and inhibit other neuronal functions in vivo and in vitro. As brain-derived neurotrophic factor, neurotrophin-4, and neurotrophin-3 are important neurotrophic factors for dopaminergic neurons, the effect of monoamine-activated alpha2M on signal transduction by trkB and trkC was investigated. The results show that monoamine-activated alpha2M binds to trkB and inhibits brain-derived neurotrophic factor/neurotrophin-4-promoted autophosphorylation of trkB in a dose-dependent manner in both trkB-expressing NIH3T3 (NIH3T3-trkB) and human neuroblastoma
Hu Y Q; Koo P H
Journal of neurochemistry
1998
1998-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Novel thiazolidinedione mitoNEET ligand-1 acutely improves cardiac stem cell survival under oxidative stress.
Animals; Cardiac/cytology/*drug effects; Cell Differentiation/drug effects; Flow Cytometry; Knockout; Male; Mice; Mitochondrial Membranes/metabolism; Mitochondrial Proteins/metabolism; Myocytes; Oxidative Stress/drug effects/*physiology; Rats; Real-Time Polymerase Chain Reaction; Stem Cells/cytology/*drug effects; Thiazolidinediones/*pharmacology; Zucker
Ischemic heart disease (IHD) is a leading cause of death worldwide, and regenerative therapies through exogenous stem cell delivery hold promising potential. One limitation of such therapies is the vulnerability of stem cells to the oxidative environment associated with IHD. Accordingly, manipulation of stem cell mitochondrial metabolism may be an effective strategy to improve survival of stem cells under oxidative stress. MitoNEET is a redox-sensitive, mitochondrial target of thiazolidinediones (TZDs), and influences cellular oxidative capacity. Pharmacological targeting of mitoNEET with the novel TZD, mitoNEET Ligand-1 (NL-1), improved cardiac stem cell (CSC) survival compared to vehicle (0.1% DMSO) during in vitro oxidative stress (H2O2). 10 muM NL-1 also reduced CSC maximal oxygen consumption rate (OCR) compared to vehicle. Following treatment with dexamethasone, CSC maximal OCR increased compared to baseline, but NL-1 prevented this effect. Smooth muscle alpha-actin expression increased significantly in CSC following differentiation compared to baseline, irrespective of NL-1 treatment. When CSCs were treated with glucose oxidase for 7 days, NL-1 significantly improved cell survival compared to vehicle (trypan blue exclusion). NL-1 treatment of cells isolated from mitoNEET knockout mice did not increase CSC survival with H2O2 treatment. Following intramyocardial injection of CSCs into Zucker obese fatty rats, NL-1 significantly improved CSC survival after 24 h, but not after 10 days. These data suggest that pharmacological targeting of mitoNEET with TZDs may acutely protect stem cells following transplantation into an oxidative environment. Continued treatment or manipulation of mitochondrial metabolism may be necessary to produce long-term benefits related to stem cell therapies.
Logan Suzanna J; Yin Liya; Geldenhuys Werner J; Enrick Molly K; Stevanov Kelly M; Carroll Richard T; Ohanyan Vahagn A; Kolz Christopher L; Chilian William M
Basic research in cardiology
2015
2015-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s00395-015-0471-z" target="_blank" rel="noreferrer noopener">10.1007/s00395-015-0471-z</a>
Inhibition of cardiac fibroblast proliferation and myofibroblast differentiation by resveratrol.
70-kDa/metabolism; Angiotensin II/pharmacology; Animals; Antioxidants/*pharmacology; Cell Differentiation/drug effects; Cell Division/drug effects; Cells; Cultured; Drug Interactions; Epidermal Growth Factor/pharmacology; Fibroblasts/*cytology/*drug effects; Male; Mitogen-Activated Protein Kinase 1/metabolism; Mitogen-Activated Protein Kinase 3/metabolism; Myocardium/*cytology; Protein-Serine-Threonine Kinases/metabolism; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins/metabolism; Rats; Resveratrol; Ribosomal Protein S6 Kinases; Signal Transduction/drug effects; Sprague-Dawley; Stilbenes/*pharmacology; Vasoconstrictor Agents/pharmacology
Cardiac fibroblasts (CFs) regulate myocardial remodeling by proliferating, differentiating, and secreting extracellular matrix proteins. Prolonged activation of CFs leads to cardiac fibrosis and reduced myocardial contractile function. Resveratrol (RES) exhibits a number of cardioprotective properties; however, the possibility that this compound affects CF function has not been considered. The current study tests whether RES directly influences the growth and proliferation of CFs and differentiation to the hypersecretory myofibroblast phenotype. Pretreatment of CFs with RES (5-25 microM) inhibited basal and ANG
Olson Erik R; Naugle Jennifer E; Zhang Xiaojin; Bomser Joshua A; Meszaros J Gary
American journal of physiology. Heart and circulatory physiology
2005
2005-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/ajpheart.00763.2004" target="_blank" rel="noreferrer noopener">10.1152/ajpheart.00763.2004</a>
Effects of FGF-2 and OP-1 in vitro on donor source cartilage for auricular reconstruction tissue engineering.
Bone Morphogenetic Protein 7/*pharmacology; Cell Differentiation/drug effects; Cells; Child; Chondrocytes; Chondrocytes/*drug effects/physiology; Congenital Abnormalities/diagnosis/*surgery; Congenital Microtia; Cultured; Ear Cartilage/surgery; Ear/*abnormalities/surgery; FGF-2; Fibroblast Growth Factor 2/*pharmacology; Humans; Male; Microtia; OP-1; Reconstructive Surgical Procedures/*methods; Reference Values; Tissue Donors; Tissue engineering; Tissue Engineering/*methods
OBJECTIVE: Microtia is a congenital partial or total loss of the external ear with current treatment approaches involving autologous construction from costal cartilage. Alternatively, tissue engineering provides possible use of normal or microtia auricular chondrocytes harvested from patients. This study investigated effects in vitro of basic fibroblast growth factor (FGF-2) and osteogenic protein 1 (OP-1) on human pediatric normal and microtia auricular chondrocytes and their potential proliferation and differentiation for cellular expansion. A working hypothesis was that FGF-2 promotes proliferation and OP-1 maintains an auricular phenotype of these cells. METHODS: Two patients, one undergoing otoplasty and one an ear construction, yielded normal and microtia auricular chondrocytes, respectively. The two donor sets of isolated chondrocytes were equally divided into four experimental cell groups. These were controls without added growth factors and cells supplemented with FGF-2, OP-1 or FGF-2/OP-1 combined. Cells were cultured 3, 5, 7, and 10 days (3 replicates/time point), counted and assayed by RT-qPCR to determine elastin and types II and III collagen gene expression. RESULTS: Compared to control counterparts, normal and microtia chondrocytes with
Shasti Mark; Jacquet Robin; McClellan Phillip; Yang Julianne; Matsushima Seika; Isogai Noritaka; Murthy Ananth; Landis William J
International journal of pediatric otorhinolaryngology
2014
2014-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.ijporl.2013.11.028" target="_blank" rel="noreferrer noopener">10.1016/j.ijporl.2013.11.028</a>