Linked Life Data

19822795

Source:http://linkedlifedata.com/resource/pubmed/id/19822795

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2009-11-20
pubmed:abstractText
Glutathione S-transferase-micro1, GSTM1, belongs to a superfamily of glutathione S-transferases that metabolizes a broad range of reactive oxygen species and xenobiotics. Across species, genetic variants that result in decreased expression of the Gstm1 gene are associated with increased susceptibility for vascular diseases, including atherosclerosis in humans. We previously identified Gstm1 as a positional candidate in our gene mapping study for susceptibility to renal vascular injury characterized by medial hypertrophy and hyperplasia of the renal vessels. To determine the role of Gstm1 in vascular smooth muscle cells (VSMCs), we isolated VSMCs from mouse aortas. We demonstrate that VSMCs from the susceptible C57BL/6 mice have reduced expression of Gstm1 mRNA and its protein product compared with that of the resistant 129 mice. After serum stimulation, C57BL/6 VSMCs proliferate and migrate at a much faster rate than 129 VSMCs. Furthermore, C57BL/6 VSMCs have higher levels of reactive oxygen species and exhibit exaggerated p38 mitogen-activated protein kinase phosphorylation after exposure to H(2)O(2). To establish causality, we show that knockdown of Gstm1 by small interfering RNA results in increased proliferation of VSMCs in a dose-dependent manner, as well as in increased reactive oxygen species levels and VSMC migration. Moreover, Gstm1 small interfering RNA causes increased p38 mitogen-activated protein kinase phosphorylation and attenuates the antiproliferative effect of Tempol. Our data suggest that Gstm1 is a novel regulator of VSMC proliferation and migration through its role in handling reactive oxygen species. Genetic variants that cause a decremental change in expression of Gstm1 may permit an environment of exaggerated oxidative stress, leading to susceptibility to vascular remodeling and atherosclerosis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1524-4563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1360-8
pubmed:dateRevised
2011-4-11
pubmed:meshHeading
pubmed-meshheading:19822795-Animals, pubmed-meshheading:19822795-Antioxidants, pubmed-meshheading:19822795-Aorta, pubmed-meshheading:19822795-Atherosclerosis, pubmed-meshheading:19822795-Cell Division, pubmed-meshheading:19822795-Cell Movement, pubmed-meshheading:19822795-Cells, Cultured, pubmed-meshheading:19822795-Cyclic N-Oxides, pubmed-meshheading:19822795-Glutathione Transferase, pubmed-meshheading:19822795-Hydrogen Peroxide, pubmed-meshheading:19822795-Mice, pubmed-meshheading:19822795-Mice, Inbred C57BL, pubmed-meshheading:19822795-Muscle, Smooth, Vascular, pubmed-meshheading:19822795-Oxidants, pubmed-meshheading:19822795-Oxidative Stress, pubmed-meshheading:19822795-Phosphorylation, pubmed-meshheading:19822795-RNA, Small Interfering, pubmed-meshheading:19822795-Reactive Oxygen Species, pubmed-meshheading:19822795-Species Specificity, pubmed-meshheading:19822795-Spin Labels, pubmed-meshheading:19822795-p38 Mitogen-Activated Protein Kinases
pubmed:year
2009
pubmed:articleTitle
Glutathione S-transferase-micro1 regulates vascular smooth muscle cell proliferation, migration, and oxidative stress.
pubmed:affiliation
University of Virginia, Box 800133, Charlottesville, VA 22908, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural