Succination of proteins by fumarate: mechanism of inactivation of glyceraldehyde-3-phosphate dehydrogenase in diabetes.
Ann N Y Acad Sci
; 1126: 272-5, 2008 Apr.
Article
en En
| MEDLINE
| ID: mdl-18448829
ABSTRACT
S-(2-succinyl)cysteine (2SC) is a chemical modification of proteins formed by a Michael addition reaction between the Krebs cycle intermediate, fumarate, and thiol groups in protein--a process known as succination of protein. Succination causes irreversible inactivation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in vitro. GAPDH was immunoprecipitated from muscle of diabetic rats, then analyzed by ultra-performance liquid chromatography-electrospray ionization-mass spectroscopy. Succination of GAPDH was increased in muscle of diabetic rats, and the extent of succination correlated strongly with the decrease in specific activity of the enzyme. We propose that 2SC is a biomarker of mitochondrial and oxidative stress in diabetes and that succination of GAPDH and other thiol proteins may provide the chemical link between glucotoxicity and the pathogenesis of diabetic complications.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Succinatos
/
Proteínas
/
Complicaciones de la Diabetes
/
Diabetes Mellitus
/
Fumaratos
/
Glucosafosfato Deshidrogenasa
Límite:
Humans
Idioma:
En
Revista:
Ann N Y Acad Sci
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos