Glucose-modulated tyrosine nitration in beta cells: targets and consequences. Arch Biochem Biophys 2009 Apr 15;484(2):221-31
Date
04/30/2009Pubmed ID
19402213Pubmed Central ID
PMC2759311DOI
10.1016/j.abb.2009.01.021Scopus ID
2-s2.0-64749111760 (requires institutional sign-in at Scopus site) 36 CitationsAbstract
Hyperglycemia, key factor of the pre-diabetic and diabetic pathology, is associated with cellular oxidative stress that promotes oxidative protein modifications. We report that protein nitration is responsive to changes in glucose concentrations in islets of Langerhans and insulinoma beta cells. Alterations in the extent of tyrosine nitration as well as the cellular nitroproteome profile correlated tightly with changing glucose concentrations. The target proteins we identified function in protein folding, energy metabolism, antioxidant capacity, and membrane permeability. Nitration of heat shock protein 60 in vitro was found to decrease its ATP hydrolysis and interaction with proinsulin, suggesting a mechanism by which protein nitration could diminish insulin secretion. This was supported by our finding of a decrease in stimulated insulin secretion following glycolytic stress in cultured cells. Our results reveal that protein tyrosine nitration may be a previously unrecognized factor in beta-cell dysfunction and the pathogenesis of diabetes.
Author List
Koeck T, Corbett JA, Crabb JW, Stuehr DJ, Aulak KSAuthor
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsChaperonin 60
Diabetes Mellitus
Glucose
Humans
Hyperglycemia
Insulin
Insulin-Secreting Cells
Insulinoma
Islets of Langerhans
Nitrates
Pancreatic Neoplasms
Prediabetic State
Tyrosine
