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Medical Biochemistry

Dartmouth College

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Full-Text Articles in Medical Sciences

A Cell Permeable Peptide Targeting The Intracellular Loop 2 Of Endothelin B Receptor Reduces Pulmonary Hypertension In A Hypoxic Rat Model, Daniel S. Green, Chamila Rupasinghe, Rod Warburton, Jamie L. Wilson, Christine O. Sallum, Linda Taylor, Achan Yatawara, Dale Mierke, Peter Polgar, Nicholas Hill Nov 2013

A Cell Permeable Peptide Targeting The Intracellular Loop 2 Of Endothelin B Receptor Reduces Pulmonary Hypertension In A Hypoxic Rat Model, Daniel S. Green, Chamila Rupasinghe, Rod Warburton, Jamie L. Wilson, Christine O. Sallum, Linda Taylor, Achan Yatawara, Dale Mierke, Peter Polgar, Nicholas Hill

Dartmouth Scholarship

Cell permeable peptides (CPP) aid cellular uptake of targeted cargo across the hydrophobic plasma membrane. CPP-mediated cargo delivery of receptor signaling motifs provides an opportunity to regulate specific receptor initiated signaling cascades. Both endothelin-1 receptors, ETA and ETB, have been targets of antagonist therapies for individuals with pulmonary arterial hypertension (PAH). These therapies have had success but have been accompanied by adverse reactions. Also, unlike the CPP which target specific signaling cascades, the antagonists target the entire function of the receptor. Using the CPP strategy of biased antagonism of the ETB receptor’s intracellular loop 2 (ICB2), we demonstrate blunting of …


A Truncation Mutation In Tbc1d4 In A Family With Acanthosis Nigricans And Postprandial Hyperinsulinemia, Satya Dash, Hiroyuki Sano, Justin J. Rochford, Robert K. Semple Jun 2009

A Truncation Mutation In Tbc1d4 In A Family With Acanthosis Nigricans And Postprandial Hyperinsulinemia, Satya Dash, Hiroyuki Sano, Justin J. Rochford, Robert K. Semple

Dartmouth Scholarship

Tre-2, BUB2, CDC16, 1 domain family member 4 (TBC1D4) (AS160) is a Rab-GTPase activating protein implicated in insulin-stimulated glucose transporter 4 (GLUT4) translocation in adipocytes and myotubes. To determine whether loss-of-function mutations in TBC1D4 might impair GLUT4 translocation and cause insulin resistance in humans, we screened the coding regions of this gene in 156 severely insulin-resistant patients. A female presenting at age 11 years with acanthosis nigricans and extreme postprandial hyperinsulinemia was heterozygous for a premature stop mutation (R363X) in TBC1D4. After demonstrating reduced expression of wild-type TBC1D4 protein and expression of the truncated protein in lymphocytes from the proband, …


Copper Chelation Represses The Vascular Response To Injury, Lazar Mandinov, Anna Mandinova, Stanimir Kyurkchiev, Dobroslav Kyurkchiev, Ivan Kehayov, Vihren Kolev, Raffaella Soldi, Cinzia Bagala, Ebo D. De Muinck, Volkhard Lindner, Mark J. Post, Michael Simons May 2003

Copper Chelation Represses The Vascular Response To Injury, Lazar Mandinov, Anna Mandinova, Stanimir Kyurkchiev, Dobroslav Kyurkchiev, Ivan Kehayov, Vihren Kolev, Raffaella Soldi, Cinzia Bagala, Ebo D. De Muinck, Volkhard Lindner, Mark J. Post, Michael Simons

Dartmouth Scholarship

The induction of an acute inflammatory response followed by the release of polypeptide cytokines and growth factors from peripheral blood monocytes has been implicated in mediating the response to vascular injury. Because the Cu2+-binding proteins IL-1alpha and fibroblast growth factor 1 are exported into the extracellular compartment in a stress-dependent manner by using intracellular Cu2+ to facilitate the formation of S100A13 heterotetrameric complexes and these signal peptideless polypeptides have been implicated as regulators of vascular injury in vivo, we examined the ability of Cu2+ chelation to repress neointimal thickening in response to injury. We observed that the oral administration of …