A5015979061- Mitochondrial Function and Pathology
- Liver Disease Diagnosis and Treatment
- Alcohol Consumption and Health Effects
- Liver physiology and pathology
- Adipose Tissue and Metabolism
- Pancreatic function and diabetes
- Protein Kinase Regulation and GTPase Signaling
- Metabolism and Genetic Disorders
- ATP Synthase and ATPases Research
- Peroxisome Proliferator-Activated Receptors
- Organ Transplantation Techniques and Outcomes
- Eicosanoids and Hypertension Pharmacology
- MicroRNA in disease regulation
- Gene Regulatory Network Analysis
- Diet, Metabolism, and Disease
- Endoplasmic Reticulum Stress and Disease
- Metabolomics and Mass Spectrometry Studies
- Neuroscience and Neuropharmacology Research
- Lipid metabolism and biosynthesis
- Metabolism, Diabetes, and Cancer
- Lipid Membrane Structure and Behavior
- Receptor Mechanisms and Signaling
- Reconstructive Surgery and Microvascular Techniques
- Ion Transport and Channel Regulation
- Cancer, Hypoxia, and Metabolism
Thomas Jefferson University
2016-2025
John Wiley & Sons (United States)
2016-2017
Sidney Kimmel Cancer Center
2014-2016
Indianapolis Zoo
2016
Institute of Cell Biology and Neurobiology
2014-2016
University of Alabama at Birmingham
2005-2010
University of Maryland, Baltimore
2010
Carolina Veterinary Specialists
2008
University of Nebraska Medical Center
2005
University of Iowa
2005
Mitogen-activated protein kinase (MAPK) cascades can operate as bistable switches residing in either of two different stable states. MAPK are often embedded positive feedback loops, which considered to be a prerequisite for behavior. Here we demonstrate that the absence any imposed regulation, bistability and hysteresis arise solely from distributive kinetic mechanism two-site phosphorylation dephosphorylation. Importantly, reported properties (MEK) phosphatase (MKP3) extracellular...
Proapoptotic proteins such as Bax, undergo translocation to the mitochondria during apoptosis, where they mediate release of intermembrane space including cytochrome c. Bax binds voltage-dependent anion channel (VDAC). VDAC is a beta-barrel protein located in outer mitochondrial membrane. In planar lipid bilayers, and form through which c can pass. Hexokinase II (HXK II) also VDAC. HXK catalyzes first step glycolysis highly expressed transformed cells, over 70% it bound mitochondria. The...
During the past decade, our knowledge of molecular mechanisms involved in growth factor signaling has proliferated almost explosively. However, kinetics and control information transfer through networks remain poorly understood. This paper combines experimental kinetic analysis computational modeling short term pattern cellular responses to epidermal (EGF) isolated hepatocytes. The data show transient tyrosine phosphorylation EGF receptor (EGFR) or sustained response patterns multiple...
Uncoupling protein 2 (UCP2) uncouples respiration from oxidative phosphorylation and may contribute to obesity through effects on energy metabolism. Because basal metabolic rate is decreased in obesity, UCP2 expression predicted be reduced. Paradoxically, hepatic of mRNA increased genetically obese (ob/ob) mice. In situ hybridization immunohistochemical analysis ob/ob livers demonstrate that are hepatocytes, which do not express lean Mitochondria isolated exhibit an H+ leak partially...
Emerging technologies have enabled the acquisition of large genomics and proteomics data sets. However, current methodologies for analysis do not permit interpretation in ways that unravel cellular networking. We propose a quantitative method determining functional interactions signaling gene networks. It can be used to explore cell systems at mechanistic level or applied within "modular" framework, which dramatically decreases number variables assayed. This is based on mathematical...
Abstract Transformed cells are highly glycolytic and overexpress hexokinase II (HXK II). HXK is capable of binding to the mitochondria through an interaction with voltage-dependent anion channel (VDAC), abundant outer mitochondrial membrane protein. The has been shown protect against loss cell viability. Akt activation inhibits apoptosis partly by promoting mitochondria, but mechanism which accomplishes this not characterized. present report shows that mediates negatively regulating activity...
Mitochondrial Ca(2+) uptake through the recently discovered Calcium Uniporter (MCU) is controlled by its gatekeeper Uptake 1 (MICU1). However, physiological and pathological role of MICU1 remains unclear. Here we show that vital for adaptation to postnatal life tissue repair after injury. knockout perinatally lethal in mice without causing gross anatomical defects. We used liver regeneration partial hepatectomy as a stress response model. Upon loss, early priming unaffected, but...
The overexpression of Bax kills cells by a mechanism that depends on induction the mitochondrial permeability transition (MPT) (Pastorino, J. G., Chen, S.-T., Tafani, M., Snyder, W., and Farber, L. (1998) Biol. Chem. 273, 7770–7775). In present study, purified, recombinant opened pore (PTP). Depending its concentration, had two distinct effects. At concentration 125 nm, caused release intermembranous proteins cytochrome c adenylate kinase from matrix sequestered calcein, effects prevented...
Cyclosporin A (CyA) and L-carnitine (LC) prevented the killing of cultured hepatocytes by anoxia rotenone but not cyanide. Neither CyA nor LC affected rate or extent loss mitochondrial membrane potential depletion ATP. Atractyloside blocked ability both to protect, D-carnitine antagonized effect that CyA. Cell cyanide was when phospholipase A2 inhibitor butacaine added together with Butacaine itself had no on cell killing. In a swelling assay isolated rat liver mitochondria having low...
The intracellular distribution of lipophilic ions and weak acids bases was studied in intact hepatocytes as indicators gradients pH membrane potential. Mitochondrial plasma potentials 161 32.8 mV (negative inside), respectively, were calculated from the accumulation triphenylmethylphosphonium (TPMP+) thiocyanate hepatocyte, assuming a two-compartment model. predominantly mitochondrial localization TPMP+ confirmed using disruption procedures that selectively break but not membrane....
Article13 November 2007Open Access Ligand-dependent responses of the ErbB signaling network: experimental and modeling analyses Marc R Birtwistle Department Chemical Engineering, University Delaware, Newark, DE, USA Pathology, Anatomy, Cell Biology, Thomas Jefferson University, Philadelphia, PA, Search for more papers by this author Mariko Hatakeyama Computational Experimental Systems Biology Group, RIKEN Genomic Sciences Center, Yokohama, Kanagawa, Japan Noriko Yumoto Babatunde A Ogunnaike...
Article7 April 2009Open Access Systems-level interactions between insulin–EGF networks amplify mitogenic signaling Nikolay Borisov Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA Search for more papers by this author Edita Aksamitiene Anatoly Kiyatkin Stefan Legewie Institute Theoretical Humboldt Berlin, Germany Jan Berkhout Maiwald Freiburg Advanced Science, University Freiburg, Nikolai P Kaimachnikov Biophysics, Russian Academy...
The short-term effects of ethanol on calcium homeostasis were studied in isolated hepatocytes. Ethanol caused a rapid transient activation phosphorylase not associated with changes cAMP levels which peaked after 20-30 s and declined slowly over period 5-10 min. Maximal was found 200 mM ethanol, significant effect observed at 25 ethanol. Similar induced by other organic solvents halothane, more hydrophobic agents being effective lower concentrations. In hepatocytes loaded the intracellular...
In the present study, tumor necrosis factor-α (TNF-α) cytotoxicity is shown to be potentiated by ethanol exposure in vitro human hepatoma cell line, HepG2, and rat primary hepatocytes. Exposure of HepG2 cells hepatocytes for 48 hours concentrations ranging between 50 100 mmol/L significantly increased TNF-α compared with treated alone. The killing was associated with, dependent on, development mitochondrial permeability transition (MPT). Two inhibitors MPT pore opening, cyclosporin A...
Grb2-associated binder 1 (GAB1) is a scaffold protein involved in numerous interactions that propagate signaling by growth factor and cytokine receptors. Here we explore silico validate vivo the role of GAB1 control mitogenic (Ras/MAPK) survival (phosphatidylinositol 3-kinase (PI3K)/Akt) stimulated epidermal (EGF). We built comprehensive mechanistic model allows for reliable predictions temporal patterns cellular responses to EGF under diverse perturbations, including different doses,...
Mitochondrial fusion is thought to be important for supporting cardiac contractility, but hardly detectable in cultured cardiomyocytes and difficult directly evaluate the heart. We overcame this obstacle through vivo adenoviral transduction with matrix-targeted photoactivatable GFP confocal microscopy. Imaging whole rat hearts indicated mitochondrial network formation activity ventricular cardiomyocytes. Promptly after isolation, showed extensive connectivity fusion, which decayed culture...