Transcriptional and post-transcriptional regulation of cGMP-dependent protein kinase (PKG-I): Pathophysiological significance

Hassan Sellak, Chung Sik Choi, Nupur B. Dey, Thomas M. Lincoln

Research output: Contribution to journalReview article

12 Citations (Scopus)

Abstract

The ability of the endothelium to produce nitric oxide, which induces generation of cyclic guanosine monophosphate (cGMP) that activates cGMP-dependent protein kinase (PKG-I), in vascular smooth muscle cells (VSMCs), is essential for the maintenance of vascular homeostasis. Yet, disturbance of this nitric oxide/cGMP/PKG-I pathway has been shown to play an important role in many cardiovascular diseases. In the last two decades, in vitro and in vivo models of vascular injury have shown that PKG-I is suppressed following nitric oxide, cGMP, cytokine, and growth factor stimulation. The molecular basis for these changes in PKG-I expression is still poorly understood, and they are likely to be mediated by a number of processes, including changes in gene transcription, mRNA stability, protein synthesis, or protein degradation. Emerging studies have begun to define mechanisms responsible for changes in PKG-I expression and have identified cis-and trans-acting regulatory elements, with a plausible role being attributed to post-translational control of PKG-I protein levels. This review will focus mainly on recent advances in understanding of the regulation of PKG-I expression in VSMCs, with an emphasis on the physiological and pathological significance of PKG-I down-regulation in VSMCs in certain circumstances.

Original languageEnglish (US)
Pages (from-to)200-207
Number of pages8
JournalCardiovascular Research
Volume97
Issue number2
DOIs
StatePublished - Feb 1 2013

Fingerprint

Cyclic GMP-Dependent Protein Kinases
Cyclic GMP
Vascular Smooth Muscle
Smooth Muscle Myocytes
Nitric Oxide
Vascular System Injuries
RNA Stability
Proteolysis
Endothelium
Blood Vessels
Intercellular Signaling Peptides and Proteins
Proteins
Homeostasis
Cardiovascular Diseases
Down-Regulation
Maintenance
Cytokines
Genes

Keywords

  • Gene
  • Post-transcription
  • Regulation
  • Transcription
  • Ubiquitination
  • Vascular smooth muscle cells
  • cGMP-dependent protein kinase
  • mRNA stability

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Transcriptional and post-transcriptional regulation of cGMP-dependent protein kinase (PKG-I) : Pathophysiological significance. / Sellak, Hassan; Choi, Chung Sik; Dey, Nupur B.; Lincoln, Thomas M.

In: Cardiovascular Research, Vol. 97, No. 2, 01.02.2013, p. 200-207.

Research output: Contribution to journalReview article

Sellak, Hassan ; Choi, Chung Sik ; Dey, Nupur B. ; Lincoln, Thomas M. / Transcriptional and post-transcriptional regulation of cGMP-dependent protein kinase (PKG-I) : Pathophysiological significance. In: Cardiovascular Research. 2013 ; Vol. 97, No. 2. pp. 200-207.
@article{b626047f7b6d476e9208809c7970b167,
title = "Transcriptional and post-transcriptional regulation of cGMP-dependent protein kinase (PKG-I): Pathophysiological significance",
abstract = "The ability of the endothelium to produce nitric oxide, which induces generation of cyclic guanosine monophosphate (cGMP) that activates cGMP-dependent protein kinase (PKG-I), in vascular smooth muscle cells (VSMCs), is essential for the maintenance of vascular homeostasis. Yet, disturbance of this nitric oxide/cGMP/PKG-I pathway has been shown to play an important role in many cardiovascular diseases. In the last two decades, in vitro and in vivo models of vascular injury have shown that PKG-I is suppressed following nitric oxide, cGMP, cytokine, and growth factor stimulation. The molecular basis for these changes in PKG-I expression is still poorly understood, and they are likely to be mediated by a number of processes, including changes in gene transcription, mRNA stability, protein synthesis, or protein degradation. Emerging studies have begun to define mechanisms responsible for changes in PKG-I expression and have identified cis-and trans-acting regulatory elements, with a plausible role being attributed to post-translational control of PKG-I protein levels. This review will focus mainly on recent advances in understanding of the regulation of PKG-I expression in VSMCs, with an emphasis on the physiological and pathological significance of PKG-I down-regulation in VSMCs in certain circumstances.",
keywords = "Gene, Post-transcription, Regulation, Transcription, Ubiquitination, Vascular smooth muscle cells, cGMP-dependent protein kinase, mRNA stability",
author = "Hassan Sellak and Choi, {Chung Sik} and Dey, {Nupur B.} and Lincoln, {Thomas M.}",
year = "2013",
month = "2",
day = "1",
doi = "10.1093/cvr/cvs327",
language = "English (US)",
volume = "97",
pages = "200--207",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Transcriptional and post-transcriptional regulation of cGMP-dependent protein kinase (PKG-I)

T2 - Pathophysiological significance

AU - Sellak, Hassan

AU - Choi, Chung Sik

AU - Dey, Nupur B.

AU - Lincoln, Thomas M.

PY - 2013/2/1

Y1 - 2013/2/1

N2 - The ability of the endothelium to produce nitric oxide, which induces generation of cyclic guanosine monophosphate (cGMP) that activates cGMP-dependent protein kinase (PKG-I), in vascular smooth muscle cells (VSMCs), is essential for the maintenance of vascular homeostasis. Yet, disturbance of this nitric oxide/cGMP/PKG-I pathway has been shown to play an important role in many cardiovascular diseases. In the last two decades, in vitro and in vivo models of vascular injury have shown that PKG-I is suppressed following nitric oxide, cGMP, cytokine, and growth factor stimulation. The molecular basis for these changes in PKG-I expression is still poorly understood, and they are likely to be mediated by a number of processes, including changes in gene transcription, mRNA stability, protein synthesis, or protein degradation. Emerging studies have begun to define mechanisms responsible for changes in PKG-I expression and have identified cis-and trans-acting regulatory elements, with a plausible role being attributed to post-translational control of PKG-I protein levels. This review will focus mainly on recent advances in understanding of the regulation of PKG-I expression in VSMCs, with an emphasis on the physiological and pathological significance of PKG-I down-regulation in VSMCs in certain circumstances.

AB - The ability of the endothelium to produce nitric oxide, which induces generation of cyclic guanosine monophosphate (cGMP) that activates cGMP-dependent protein kinase (PKG-I), in vascular smooth muscle cells (VSMCs), is essential for the maintenance of vascular homeostasis. Yet, disturbance of this nitric oxide/cGMP/PKG-I pathway has been shown to play an important role in many cardiovascular diseases. In the last two decades, in vitro and in vivo models of vascular injury have shown that PKG-I is suppressed following nitric oxide, cGMP, cytokine, and growth factor stimulation. The molecular basis for these changes in PKG-I expression is still poorly understood, and they are likely to be mediated by a number of processes, including changes in gene transcription, mRNA stability, protein synthesis, or protein degradation. Emerging studies have begun to define mechanisms responsible for changes in PKG-I expression and have identified cis-and trans-acting regulatory elements, with a plausible role being attributed to post-translational control of PKG-I protein levels. This review will focus mainly on recent advances in understanding of the regulation of PKG-I expression in VSMCs, with an emphasis on the physiological and pathological significance of PKG-I down-regulation in VSMCs in certain circumstances.

KW - Gene

KW - Post-transcription

KW - Regulation

KW - Transcription

KW - Ubiquitination

KW - Vascular smooth muscle cells

KW - cGMP-dependent protein kinase

KW - mRNA stability

UR - http://www.scopus.com/inward/record.url?scp=84872538931&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84872538931&partnerID=8YFLogxK

U2 - 10.1093/cvr/cvs327

DO - 10.1093/cvr/cvs327

M3 - Review article

C2 - 23139241

AN - SCOPUS:84872538931

VL - 97

SP - 200

EP - 207

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 2

ER -