S-Nitrosation of monocarboxylate transporter 1: inhibition of pyruvate-fueled respiration and proliferation of breast cancer cells.
Free Radic Biol Med
; 69: 229-38, 2014 Apr.
Article
en En
| MEDLINE
| ID: mdl-24486553
Energy substrates metabolized through mitochondria (e.g., pyruvate, glutamine) are required for biosynthesis of macromolecules in proliferating cells. Because several mitochondrial proteins are known to be targets of S-nitrosation, we determined whether bioenergetics are modulated by S-nitrosation and defined the subsequent effects on proliferation. The nitrosating agent S-nitroso-L-cysteine (L-CysNO) was used to initiate intracellular S-nitrosation, and treatment decreased mitochondrial function and inhibited proliferation of MCF7 mammary adenocarcinoma cells. Surprisingly, the d-isomer of CysNO (D-CysNO), which is not transported into cells, also caused mitochondrial dysfunction and limited proliferation. Both L- and D-CysNO also inhibited cellular pyruvate uptake and caused S-nitrosation of thiol groups on monocarboxylate transporter 1, a proton-linked pyruvate transporter. These data demonstrate the importance of mitochondrial metabolism in proliferative responses in breast cancer and highlight a novel role for inhibition of metabolic substrate uptake through S-nitrosation of exofacial protein thiols in cellular responses to nitrosative stress.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Nitrosación
/
Ácido Pirúvico
/
Transportadores de Ácidos Monocarboxílicos
/
Simportadores
/
Mitocondrias
Límite:
Humans
Idioma:
En
Revista:
Free Radic Biol Med
Asunto de la revista:
BIOQUIMICA
/
MEDICINA
Año:
2014
Tipo del documento:
Article
Pais de publicación:
Estados Unidos