Signal transducer and activator of transcription 3α and specificity protein 1 interact to upregulate intercellular adhesion molecule-1 in ischemic-reperfused myocardium and vascular endothelium

Xiao Ping Yang; Kaikobad IRANI; Subhendra MATTAGAJASINGH; Anthony DIPAULA; Firdous KHANDAY; Michitaka OZAKI; Karen FOX-TALBOT; William M BALDWIN; Lewis C BECKER

doi:10.1161/01.ATV.0000168428.96177.24

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Signal transducer and activator of transcription 3α and specificity protein 1 interact to upregulate intercellular adhesion molecule-1 in ischemic-reperfused myocardium and vascular endothelium

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Signal transducer and activator of transcription 3α and specificity protein 1 interact to upregulate intercellular adhesion molecule-1 in ischemic-reperfused myocardium and vascular endothelium

Xiao Ping Yang, Kaikobad IRANI, Subhendra MATTAGAJASINGH, Anthony DIPAULA, Firdous KHANDAY, Michitaka OZAKI, Karen FOX-TALBOT, William M BALDWIN and Lewis C BECKER

Arteriosclerosis, thrombosis, and vascular biology, Vol.25(7), pp.1395-1400

2005

DOI: 10.1161/01.ATV.0000168428.96177.24

PMID: 15860735

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Abstract

Objective— Intercellular adhesion molecule-1 (ICAM-1) is upregulated rapidly on endothelial cells during ischemia–reperfusion (I-R) and mediates tissue leukocyte accumulation. The ICAM-1 proximal promoter contains a signal transducer and activator of transcription (Stat) binding motif (gamma-interferon activation site [GAS] sequence), which flanks a specificity protein 1 (Sp1) binding site. We examined the roles of Stat and Sp1 in the regulation of ICAM-1 after myocardial I-R. Methods and Results— Open-chest anesthetized rats underwent coronary artery occlusion for 35 minutes and reperfusion for 0 to 240 minutes. Stat became activated within 15 minutes after reperfusion, primarily in vascular endothelial cells; the activated Stat protein was identified as Stat3 (α-isoform). After phosphorylation on serine 727 (p-S727), Stat3α was found in association with the transcriptional regulator Sp1, and the complex bound to an ICAM-1–GAS probe. ICAM-1 expression increased after I-R and lagged shortly behind Stat3α activation. In cultured human umbilical vein endothelial (HUVE) cells, activation of Stat3α after hypoxia–reoxygenation (H-R) was dependent on the small GTPase Rac1. Transfection of a dominant-negative Stat3 (Y705F) adenovirus or a GAS decoy oligonucleotide reduced ICAM-1 mRNA expression after H-R. Using a reporter gene transfected into HUVE cells, mutation of the GAS element in the ICAM-1 promoter resulted in reduced transcriptional activity after H-R. Sp1 coimmunoprecipitated with p-S727 Stat3 during H-R, and Sp1 or Stat3α interfering RNA markedly reduced ICAM-1 mRNA expression. Conclusion— The Sp1–Stat3 complex appears to play an important role in the upregulation of ICAM-1 transcription after reoxygenation or reperfusion.

Diabetes. Impaired glucose tolerance

Blood vessels and receptors

Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous

Atherosclerosis (general aspects, experimental research)

Biological and medical sciences

Medical sciences

Vertebrates: cardiovascular system

Endocrine pancreas. Apud cells (diseases)

Fundamental and applied biological sciences. Psychology

Cardiology. Vascular system

Endocrinopathies

Blood and lymphatic vessels

Associated diseases and complications

Details

Title: Subtitle: Signal transducer and activator of transcription 3α and specificity protein 1 interact to upregulate intercellular adhesion molecule-1 in ischemic-reperfused myocardium and vascular endothelium
Creators: Xiao Ping Yang - Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md, United States
Kaikobad IRANI - Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md, United States
Subhendra MATTAGAJASINGH - Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md, United States
Anthony DIPAULA - Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md, United States
Firdous KHANDAY - Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md, United States
Michitaka OZAKI - Department of Surgery, Division of Organ Transplantation and Regenerative Medicine, Hokkaido University Graduate School of Medicine, Japan
Karen FOX-TALBOT - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Md, United States
William M BALDWIN - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Md, United States
Lewis C BECKER - Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md, United States
Resource Type: Journal article
Publication Details: Arteriosclerosis, thrombosis, and vascular biology, Vol.25(7), pp.1395-1400
DOI: 10.1161/01.ATV.0000168428.96177.24
PMID: 15860735
NLM abbreviation: Arterioscler Thromb Vasc Biol
ISSN: 1079-5642
eISSN: 1524-4636
Publisher: Lippincott; Philadelphia, PA; Hagerstown, MD
Language: English
Date published: 2005
Academic Unit: Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
Record Identifier: 9984047895602771

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