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Published on: September 6, 2015
Sulfated and Glucuronidated Conjugates of 3-(4-Hydroxy-3-methoxyphenyl) Propionic Acid Can Promote NO Production by
Tint Ni Ni Tun1, Susumu Yoshino2, Hiroyuki Kayaki2
1Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
Abstract:
We aimed to clarify whether metabolic conjugates of sulfated and glucuronidated forms have the physiological potential to produce the vasorelaxant nitric oxide (NO) in human umbilical vein endothelial cells (HUVECs), using 3-(4-hydroxy-3-methoxyphenyl) propionic acid (HMPA), a metabolite of dietary flavonoids in the gut. Treatment of HUVECs with sulfated and glucuronidated HMPAs significantly increased NO production and eNOS phosphorylation. A transporter-inhibitor-aided cellular uptake experiment of HMPAs revealed that both conjugates were incorporated into cells via MCT, OATP1A2, and GLUT transporters, whereas intact HMPA was transported via the MCT and OATP1A2 routes. A Fluo-4-probe Ca2+ assay demonstrated that the incorporated HMPAs significantly increased intracellular Ca2+ concentration by stimulating the IP3R of the endoplasmic reticulum in the CaMKII/eNOS signaling cascade. In conclusion, to our knowledge, this study provides the first evidence that sulfated and glucuronidated forms of HMPAs may stimulate NO production in HUVECs.
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