Oxidative stress is the central cause of angiotensin II (Ang II)-induced myocardial injury, and nuclear factor erythroid 2-related factor (Nrf2) is the core molecule of the anti-oxidant defense system. We have previously demonstrated that sulforaphane (SFN) can prevent Ang II-induced myocardial injury by activating Nrf2; however, the underlying molecular mechanism is still unclear. This study aimed to evaluate whether SFN prevents Ang II-induced cardiomyocyte apoptosis through acetylation modification of Nrf2. Wild-type and Nrf2 knockdown embryonic rat cardiomyocytes (H9C2) were exposed to Ang II to induce apoptosis, oxidative stress, and inflammatory responses. SFN treatment significantly reduced Ang II-induced cardiomyocyte apoptosis, inflammation and oxidative stress. Activation of Nrf2 played a critical role in preventing cardiomyocyte apoptosis. After Nrf2 was knockdown, the anti-inflammatory, antioxidant stress of SFN were eliminated. Furthermore, Nrf2 activation by SFN was closely related to the decreased activity of histone deacetylases (HDACs) and increased histone-3 (H3) acetylation levels in Nrf2 promoter region. These findings confirm that Nrf2 plays a key role in SFN preventing Ang II-induced cardiomyocyte apoptosis. SFN activates Nrf2 by inhibiting HDACs expression and activation.
Keywords: angiotensin II; nuclear factor erythroid 2-related factor; oxidative stress; sulforaphane.