Sesamin Induces Endothelial Nitric Oxide Synthase Activation via Transient Receptor Potential Vanilloid Type 1

• Published in: Journal of agricultural and food chemistry 2020-03, Vol.68 (11), p.3474-3484
• Main Authors: Pham, Thi Hoa, Jin, Sun Woo, Lee, Gi Ho, Park, Jin Song, Kim, Ji Yeon, Thai, Tuyet Ngan, Han, Eun Hee, Jeong, Hye Gwang
• Format: Article
• Language: English
• Subjects: AMP-Activated Protein Kinases - genetics; AMP-Activated Protein Kinases - metabolism; Dioxoles - pharmacology; Endothelial Cells - metabolism; Lignans - pharmacology; Nitric Oxide; Nitric Oxide Synthase Type III - genetics; Nitric Oxide Synthase Type III - metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.9b07909

Sesamin, the most abundant lignan in sesame seed oil, has many biological activities. However, the underlying molecular mechanisms behind the regulatory effects of sesamin on endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) generation in endothelial cells (ECs) remain unclear. Sesamin induced the intracellular level of NO and eNOS phosphorylation in ECs in a concentration- and time-dependent manner. Additionally, sesamin induced levels of intracellular calcium, leading to the phosphorylation of calmodulin-dependent protein kinase II (CaMKII) at Thr286, calcium/calmodulin-dependent protein kinase kinase beta (CaMKKβ) at Ser511, protein kinase A (PKA) at Thr197, Akt at Ser473, and AMP-activated protein kinase (AMPK) at Thr172. In particular, blocking of the transient receptor potential vanilloid type 1 (TRPV1) channel by capsazepine (TRPV1 antagonist), as well as TRPV1 knockdown via TRPV1 silencing RNA, abrogated sesamin-induced PKA, Akt, AMPK, CaMKII, CaMKKβ, and eNOS phosphorylation and NO level in ECs. Furthermore, sesamin inhibited TNF-α-induced NF-κB translocation, intercellular adhesion molecule-1 expression, and monocyte adhesion. Sesamin triggered eNOS activity and NO production via activation of TRPV1-calcium signaling, which involved the phosphorylation of PKA, CaMKII, CaMKKβ, Akt, and AMPK. Sesamin may be useful for treating or preventing the endothelial dysfunction correlated with cardiovascular diseases.