Induction of lung glutathione and glutamylcysteine ligase by 1,4-phenylenebis(methylene)selenocyanate and its glutathione conjugate: role of nuclear factor-erythroid 2-related factor 2

Autor: Shantu Amin, Karam El-Bayoumy, Dhimant Desai, John P. Richie, Sans W. Emmert, Cesar Aliaga, Yuan-Wan Sun, Arunangshu Das
Rok vydání: 2011
Předmět:
Zdroj: Free radical biologymedicine. 52(10)
ISSN: 1873-4596
Popis: The synthetic organoselenium agent 1,4-phenylenebis(methylene)selenocyanate (p-XSC) and its glutathione (GSH) conjugate (p-XSeSG) are potent chemopreventive agents in several preclinical models. p-XSC is also an effective inducer of GSH in mouse lung. Our objectives were to test the hypothesis that GSH induction by p-XSC occurs through upregulation of the rate-limiting GSH biosynthetic enzyme glutamylcysteine ligase (GCL), through activation of antioxidant response elements (AREs) in GCL genes via activation of nuclear factor-erythroid 2-related factor 2 (Nrf2). p-XSC feeding (10 ppm Se) increased GSH (230%) and upregulated the catalytic subunit of GCL (GCLc) (55%), extracellular-related kinase (220%), and nuclear Nrf2 (610%) in lung but not liver after 14 days in the rat (P
Databáze: OpenAIRE