AIM OF THE STUDY: Gomisin A (GA) is a small molecular weight lignan contained in Fructus Schisandrae, the dried seed of Schisandra chinensis which is widely used as a tonic in traditional Korean medicine. We previously demonstrated that GA induces endothelium-dependent and -independent relaxation in rat thoracic aorta, however the signaling pathways involved was not clarified. In this study, we examined whether GA could actually induce nitric oxide (NO) production and clarified the mechanism in cultured human coronary artery endothelial cells (HCAEC). RESULTS: Treatment of HCAEC with GA induced NO production in a time- and concentration-dependent manner in association with an enhanced endothelial NO synthase (eNOS) activity with an increased cytosolic translocation of eNOS. Both GA-induced NO production and eNOS activation were attenuated by pretreatment of the cells with EGTA, an extracellular Ca(2+) chelator, and BAPTA-AM, an intracellular Ca(2+) chelator, but not by LY 294002, a PI3-kinase/Akt inhibitor, suggesting involvement of Ca(2+). Furthermore, GA rapidly increased the intracellular Ca(2+) concentration, which was abolished in Ca(2+) free media. CONCLUSION: Taken together, our results suggest that GA induces Ca(2+)-dependent activation and translocation of eNOS in HCAEC, events linked to NO production and thereby endothelial-dependent vasorelaxation.
AIM OF THE STUDY: Gomisin A (GA) is a small molecular weight lignan contained in Fructus Schisandrae, the dried seed of Schisandra chinensis which is widely used as a tonic in traditional Korean medicine. We previously demonstrated that GA induces endothelium-dependent and -independent relaxation in rat thoracic aorta, however the signaling pathways involved was not clarified. In this study, we examined whether GA could actually induce nitric oxide (NO) production and clarified the mechanism in cultured human coronary artery endothelial cells (HCAEC). RESULTS: Treatment of HCAEC with GA induced NO production in a time- and concentration-dependent manner in association with an enhanced endothelial NO synthase (eNOS) activity with an increased cytosolic translocation of eNOS. Both GA-induced NO production and eNOS activation were attenuated by pretreatment of the cells with EGTA, an extracellular Ca(2+) chelator, and BAPTA-AM, an intracellular Ca(2+) chelator, but not by LY 294002, a PI3-kinase/Akt inhibitor, suggesting involvement of Ca(2+). Furthermore, GA rapidly increased the intracellular Ca(2+) concentration, which was abolished in Ca(2+) free media. CONCLUSION: Taken together, our results suggest that GA induces Ca(2+)-dependent activation and translocation of eNOS in HCAEC, events linked to NO production and thereby endothelial-dependent vasorelaxation.
Authors: Young Mi Seok; Young Whan Choi; Gyung-Duck Kim; Hye Young Kim; Yoh Takuwa; In Kyeom Kim Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2010-10-31 Impact factor: 3.000
Authors: Ji Young Park; Jung Wook Yun; Young Whan Choi; Jin Ung Bae; Kyo Won Seo; Seung Jin Lee; So Youn Park; Ki Whan Hong; Chi Dae Kim Journal: Hypertens Res Date: 2012-04-26 Impact factor: 3.872