This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Insufficient energy production, impaired DNA repairing and smooth muscle cell (SMC) apoptosis are hallmarks of advanced atherosclerotic plaque. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a multifunctional glycolytic enzyme that plays an important role in energy production. GAPDH also protects the cell genome integrity and oxidative stress-modified GAPDH initiates the cell apoptosis. The major hypothesis of this project that restoring GAPDH levels in SMC would be protective against oxidant-induced apoptosis and suppression of cell migration in vitro and against diet-induced atherosclerosis in vivo. We will determine if manipulation of GAPDH levels in SMC with/without oxidant would be translated into adequate changes in cell migration and apoptosis. Since progressive DNA damage is associated with atherosclerosis progression, we plan to study if GAPDH plays a protective role in oxidant-induced DNA damage in SMC. We also plan to test if restoring GAPDH levels in atherosclerotic SMC would stimulate cell energy production and leads to a reduction in atherosclerosis.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR018766-09
Application #
8360498
Study Section
Special Emphasis Panel (ZRR1-RI-6 (01))
Project Start
2011-07-01
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
9
Fiscal Year
2011
Total Cost
$280,814
Indirect Cost
Name
Louisiana State Univ Hsc New Orleans
Department
Pharmacology
Type
Schools of Medicine
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
Li, Li; Bai, Shi; Sheline, Christian T (2017) hZnT8 (Slc30a8) Transgenic Mice That Overexpress the R325W Polymorph Have Reduced Islet Zn2+ and Proinsulin Levels, Increased Glucose Tolerance After a High-Fat Diet, and Altered Levels of Pancreatic Zinc Binding Proteins. Diabetes 66:551-559
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