Transduction of phosphorylated heat shock-related protein 20, HSP20, prevents vasospasm of human umbilical artery smooth muscle

1 The Biodesign Institute, Arizona State University, Tempe; 2 Department of Surgery, Mayo Clinic Scottsdale, Scottsdale; and 3 Carl T. Hayden Veterans Affairs Medical Center, Phoenix, Arizona Submitted 21 September 2004 ; accepted in final form 22 December 2004 Activation of cyclic nucleotide-depend...

Full description

Saved in:
Bibliographic Details
Published in:Journal of applied physiology (1985) 2005-05, Vol.98 (5), p.1836-1845
Main Authors: Flynn, Charles R, Brophy, Colleen M, Furnish, Elizabeth J, Komalavilas, Padmini, Tessier, Deron, Thresher, Jeffrey, Joshi, Lokesh
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Biological and medical sciences
Blood vessels
Female
Fundamental and applied biological sciences. Psychology
Gene Transfer Techniques
Heat
Heat-Shock Proteins - biosynthesis
Heat-Shock Proteins - genetics
Heat-Shock Proteins - therapeutic use
HSP20 Heat-Shock Proteins
Humans
In Vitro Techniques
Molecular Sequence Data
Muscle, Smooth, Vascular - metabolism
Muscular system
Peptide Fragments - biosynthesis
Peptide Fragments - genetics
Phosphoproteins - biosynthesis
Phosphoproteins - genetics
Phosphoproteins - therapeutic use
Phosphorylation
Proteins
Umbilical Arteries - metabolism
Vasoconstriction - genetics
Vasoconstriction - physiology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:1 The Biodesign Institute, Arizona State University, Tempe; 2 Department of Surgery, Mayo Clinic Scottsdale, Scottsdale; and 3 Carl T. Hayden Veterans Affairs Medical Center, Phoenix, Arizona Submitted 21 September 2004 ; accepted in final form 22 December 2004 Activation of cyclic nucleotide-dependent signaling pathways inhibits agonist-induced contraction of most vascular smooth muscles except human umbilical artery smooth muscle (HUASM). This impaired vasorelaxation may contribute to complications associated with preeclampsia, intrauterine growth restriction, and preterm delivery. Cyclic nucleotide-dependent signaling pathways converge at the phosphorylation of the small heat shock-related protein HSP20, causing relaxation of vascular smooth muscle. We produced recombinant proteins containing a protein transduction domain linked to HSP20 (rTAT-HSP20). Pretreatment of HUASM with in vitro phosphorylated rTAT-HSP20 (rTAT-pHSP20) significantly inhibited serotonin-induced contraction, without a decrease in myosin light chain phosphorylation. rTAT-pHSP20 remained phosphorylated upon transduction into isolated HUASM as demonstrated by two-dimensional gel electrophoresis. Transduction of peptide analogs of phospho-HSP20 containing the phosphorylation site on HSP20 and phosphatase-resistant mimics of the phosphorylation site (S16E) also inhibited HUASM contraction. These data suggest that impaired relaxation of HUASM may result from decreased levels of phosphorylated HSP20. Protein transduction can be used to restore intracellular expression levels and the associated physiological response. Transduction of posttranslationally modified substrate proteins represents a proteomic-based therapeutic approach that may be particularly useful when the expression of downstream substrate proteins is downregulated. human umbilical artery smooth muscle; phosphorylation; protein transduction; myosin light chain; mass spectrometry Address for reprint requests and other correspondence: C. M. Brophy, The Biodesign Institute, Arizona State Univ., Tempe, AZ 85287-9709 (E-mail: colleen.brophy{at}asu.edu )
ISSN:8750-7587
1522-1601
DOI:10.1152/japplphysiol.01043.2004