Honokiol ameliorates angiotensin II-induced hypertension and endothelial dysfunction by inhibiting HDAC6-mediated cystathionine γ-lyase degradation
| Autor: | Sang Yoon Lee, Dongsoo Kim, Zhexi Chi, Sook Young Lee, Sang Ki Lee, Erling Guo, Jae Hyung Kim, Seung-Yong Seo, Truc Phan Hoang Le, Sanha Lee |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Honokiol Male Proteasome Endopeptidase Complex Lysine Pharmacology Histone Deacetylase 6 Lignans 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Ubiquitin parasitic diseases medicine Animals Humans Hydrogen Sulfide Endothelial dysfunction Aorta biology Chemistry Angiotensin II Biphenyl Compounds Cystathionine gamma-Lyase Endothelial Cells Acetylation Cell Biology HDAC6 medicine.disease Cystathionine beta synthase Recombinant Proteins Mice Inbred C57BL 030104 developmental biology HEK293 Cells 030220 oncology & carcinogenesis Hypertension Proteolysis biology.protein Molecular Medicine Protein Processing Post-Translational |
| Zdroj: | Journal of cellular and molecular medicine. 24(18) |
| ISSN: | 1582-4934 |
| Popis: | Hypertension and endothelial dysfunction are associated with various cardiovascular diseases. Hydrogen sulphide (H2 S) produced by cystathionine γ-lyase (CSE) promotes vascular relaxation and lowers hypertension. Honokiol (HNK), a natural compound in the Magnolia plant, has been shown to retain multifunctional properties such as anti-oxidative and anti-inflammatory activities. However, a potential role of HNK in regulating CSE and hypertension remains largely unknown. Here, we aimed to demonstrate that HNK co-treatment attenuated the vasoconstriction, hypertension and H2 S reduction caused by angiotensin II (AngII), a well-established inducer of hypertension. We previously found that histone deacetylase 6 (HDAC6) mediates AngII-induced deacetylation of CSE, which facilitates its ubiquitination and proteasomal degradation. Our current results indicated that HNK increased endothelial CSE protein levels by enhancing its stability in a sirtuin-3-independent manner. Notably, HNK could increase CSE acetylation levels by inhibiting HDAC6 catalytic activity, thereby blocking the AngII-induced degradative ubiquitination of CSE. CSE acetylation and ubiquitination occurred mainly on the lysine 73 (K73) residue. Conversely, its mutant (K73R) was resistant to both acetylation and ubiquitination, exhibiting higher protein stability than that of wild-type CSE. Collectively, our findings suggested that HNK treatment protects CSE against HDAC6-mediated degradation and may constitute an alternative for preventing endothelial dysfunction and hypertensive disorders. |
| Databáze: | OpenAIRE |
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