Document Detail


Differential activation of mitogenic signaling pathways in aortic smooth muscle cells deficient in superoxide dismutase isoforms.
MedLine Citation:
PMID:  15746439     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Reactive oxygen species (ROS) integrate cellular signaling pathways involved in aortic smooth muscle cell (SMC) proliferation and migration associated with atherosclerosis. However, the effect of subcellular localization of ROS on SMC mitogenic signaling is not yet fully understood.
METHODS AND RESULTS: We used superoxide dismutase (SOD)-deficient mouse aortic SMCs to address the role of subcellular ROS localization on SMC phenotype and mitogenic signaling. Compared with wild-type, a 54% decrease in total SOD activity (almost equal to 50% decrease in SOD1 protein levels) and a 42% reduction in SOD2 activity (approximately equal to 50% decrease in SOD2 protein levels) were observed in SOD1+/- and SOD2+/- SMCs, respectively. Consistent with this, basal and thrombin-induced superoxide levels increased in these SMCs. SOD1+/- and SOD2+/- SMCs exhibit increased basal proliferation and enhanced [3H]-thymidine and [3H]-leucine incorporation in basal and thrombin-stimulated conditions. Our results indicate preferential activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinases in SOD1+/- and janus kinase/signal transducer and activator of transcriptase (JAK/STAT) pathway in SOD2+/- SMCs. Pharmacological inhibitors of ERK1/2 p38 and JAK2 confirm the SOD genotype-dependent SMC proliferation.
CONCLUSIONS: Our results suggest that SOD1 and SOD2 regulate SMC quiescence by suppressing divergent mitogenic signaling pathways, and dysregulation of these enzymes under pathophysiological conditions may lead to SMC hyperplasia and hypertrophy.
Authors:
Nageswara R Madamanchi; Sung-Kwon Moon; Zeenat S Hakim; Shantres Clark; Ali Mehrizi; Cam Patterson; Marschall S Runge
Related Documents :
10477139 - Short-term pravastatin mediates growth inhibition and apoptosis, independently of ras, ...
16630729 - Stromal cell derived factor-1 acutely promotes neural progenitor cell proliferation in ...
16769879 - Requirement of nck adaptors for actin dynamics and cell migration stimulated by platele...
9144559 - Regulation by camp of stat1 activation in hepatic stellate cells.
15502039 - The inhibition of aortic smooth muscle cell proliferation by the intravenous anesthetic...
1352989 - Extracellular calcium mimics the actions of platelet-derived growth factor on mouse fib...
12888899 - Prognostic relevance of mapk expression in glioblastoma multiforme.
14871479 - Hocl-mediated cell death and metabolic dysfunction in the yeast saccharomyces cerevisiae.
7824169 - Localization of protein kinase c subspecies in the rabbit retina.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.     Date:  2005-03-03
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  25     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-05-02     Completed Date:  2005-12-29     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  950-6     Citation Subset:  IM    
Affiliation:
Carolina Cardiovascular Biology Center, Department of Medicine, University of North Carolina, Chapel Hill 27599-7005, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Aorta / enzymology,  pathology
Atherosclerosis / metabolism*,  pathology
Cell Compartmentation / physiology
Cell Division / drug effects,  physiology
Cells, Cultured
Enzyme Inhibitors / pharmacology
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors,  metabolism
Gene Expression Regulation, Enzymologic
Hypertrophy
Janus Kinase 2
MAP Kinase Signaling System / drug effects,  physiology*
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Muscle, Smooth, Vascular / enzymology*,  pathology
Protein-Tyrosine Kinases / antagonists & inhibitors,  metabolism
Proto-Oncogene Proteins / antagonists & inhibitors,  metabolism
Reactive Oxygen Species / metabolism
STAT3 Transcription Factor / metabolism
Superoxide Dismutase / genetics,  metabolism*
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism
Grant Support
ID/Acronym/Agency:
AG-21096/AG/NIA NIH HHS; HL-57352/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Proto-Oncogene Proteins; 0/Reactive Oxygen Species; 0/STAT3 Transcription Factor; 0/Stat3 protein, mouse; EC 1.15.1.-/superoxide dismutase 1; EC 1.15.1.1/Superoxide Dismutase; EC 1.15.1.1/superoxide dismutase 2; EC 2.7.10.1/Janus Kinase 2; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.2/Jak2 protein, mouse; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases
Comments/Corrections
Comment In:
Arterioscler Thromb Vasc Biol. 2005 May;25(5):887-8   [PMID:  15863719 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Association between serum uric acid, metabolic syndrome, and carotid atherosclerosis in Japanese ind...
Next Document:  NO generation from nitrite and its role in vascular control.