S-1-Propenylcysteine augments BACH1 degradation and heme oxygenase 1 expression in a nitric oxide-dependent manner in endothelial cells

Publication date: Available online 8 January 2019Source: Nitric OxideAuthor(s): Tadamitsu Tsuneyoshi, Kayo Kunimura, Naoaki MoriharaAbstractGarlic has been demonstrated to exert protective effects against oxidative damage using numerous experimental models. The antioxidant effects of garlic are associated with the activation of Nrf2-dependent gene expression. S-1-Propenylcysteine (S1PC) and S-allylcysteine (SAC) are two predominant sulfur amino acids present in aged garlic extract; however, the exact roles of these amino acids within the Keap1/Nrf2 system remain unknown. We hypothesized that sulfur-containing amino acids derived from garlic could activate Nrf2 in the presence of nitric oxide (NO). Neither S1PC nor SAC affected gene expression of either heme oxygenase-1 (HMOX1) or the glutamate-cysteine ligase modifier subunit (GCLM) in human umbilical vein endothelial cells (HUVECs) or human aorta endothelial cells (HAECs). Interestingly, S1PC augmented expression levels induced by nitric oxide donors (NO-donors) such as NOR3 and GSNO. NO-donors were found to induce nuclear accumulation of NRF2 and activation of the eIF2α/ATF4 pathway, whereas S1PC did not further amplify the NO-induced effects on NRF2 or eIF2α/ATF4. Additionally, NO-donors induced the degradation of BTB domain and CNC homolog 1 (BACH1), a transcriptional repressor that can compete with NRF2. In addition, S1PC enhanced BACH1 downregulation within the nucleus. Pretreatment with deferoxamine, an inhibitor of ...
Source: Nitric Oxide - Category: Chemistry Source Type: research