Hypertension and endothelial dysfunction are associated with various cardiovascular diseases. Cystathionine γ-lyase (CSE) is an enzyme that produces hydrogen sulfide (H2S). Endothelial H2S production promotes vascular relaxation, supporting to the alleviation of hypertension. Honokiol (HNK) is a natural compound in the Magnolia plant, has been shown to retain multifunctional attributes such as anti-oxidant and anti-inflammatory activity. However, a potential role of HNK in mediating CSE and hypertension remains mostly unknown. Here, We directed to indicate that HNK cotreatment attenuated the hypertension, vasoconstriction, and H2S reduction caused by angiotensin II (AngII), a well-induced inducer of hypertension. Recent studies the part of histone deacetylase 6 (HDAC6) in hypertension has been recommend, but the underlying mechanisms are poorly understood. We found that tubastatin A the HDAC6 inhibitor attenuates angiotensin II induced hypertension by preventing CSE protein degradation. Our results indicate that HNK could improve CSE acetylation levels by inhibiting HDAC6 catalytic activity, By blocking the AngII-induced degradative ubiquitination of CSE. CSE acetylation and ubiquitination happened mainly on the lysine 73 (K73) residue. Conversely, its mutant (K73R) was against to both acetylation and ubiquitination, expressing higher protein stability than that of wild-type CSE. Overall, this study recommend that HNK treatment protects CSE against HDAC6-mediated degradation and may comprise an alternative for preventing endothelial dysfunction and hypertension.
