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.
authors.affiliation: Department of Physiology, College of Medicine, University of South Alabama, Medical Science Building Room 3103, Mobile, AL 36688, USA. hsellak@usouthal.edu
authors.forename: Hassan
authors.initials: H
authors.lastname: Sellak
authors.forename: Chung-sik
authors.initials: CS
authors.lastname: Choi
authors.forename: Nupur B
authors.initials: NB
authors.lastname: Dey
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Lincoln
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D062965:Cyclic GMP-Dependent Protein Kinase Type I / Q000235:genetics* / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D062965:Cyclic GMP-Dependent Protein Kinase Type I