title: Resveratrol analog piceatannol restores the palmitic acid-induced impairment of insulin signaling and production of endothelial nitric oxide via activation of anti-inflammatory and antioxidative heme oxygenase-1 in human endothelial cells.
abstract: Growing evidence suggests that the elevation of free fatty acids, including palmitic acid (PA), are associated with inflammation and oxidative stress, which may be involved in endothelial dysfunction, characterized by the reduced bioavailability of nitric oxide (NO) synthesized from endothelial NO synthase (eNOS). Heme oxygenase-1 (HO-1) is important in the preservation of NO bioavailability. Piceatannol (Pic), with similar chemical structure to resveratrol, is suggested to possess similar protective effects as resveratrol. In the present study, human umbilical vein endothelial cells (HUVECs), stimulated with PA, were used to examine the endothelial protective effects of Pic. Pic increased the expression of HO-1 via nuclear factor erythroid-2-related factor-2 activation in the HUVECs, and decreased the PA-induced secretions of interleukin-6 and tumor necrosis factor-α, and the formation of reactive oxygen species ROS via inhibition of NF-κB activation. Notably, following inhibition of HO-1 activity by tin protoporphryin-IX, Pic did not prevent cytokine secretion, ROS formation, and NF-κB activation in the PA-stimulated HUVECs. PA attenuated insulin-mediated insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, leading to decreased glucose uptake, and phosphorylation of eNOS, leading to a reduction in the production of NO. Pic effectively mitigated the inhibitory effects of PA on the insulin-mediated phosphorylation of IRS-1 and eNOS, which was not observed following inhibition of HO‑1 activity. The results of the present study suggested that Pic may have the potential to prevent PA-induced impairment of insulin signaling and eNOS function, by inducing the expression of the anti-inflammatory and antioxidant, HO-1.
authors: Department of Microbiology and Immunology, Wonkwang University School of Medicine, Iksan 570‑749, Republic of Korea.
authors: Sun-Oh
authors: SO
authors: Jeong
authors: Department of Anesthesiology and Pain Medicine, Wonkwang University School of Medicine, Iksan 570‑749, Republic of Korea.
authors: Yong
authors: Y
authors: Son
authors: Department of Anesthesiology and Pain Medicine, Wonkwang University School of Medicine, Iksan 570‑749, Republic of Korea.
authors: Ju Hwan
authors: JH
authors: Lee
authors: Department of Anesthesiology and Pain Medicine, Wonkwang University School of Medicine, Iksan 570‑749, Republic of Korea.
authors: Yong-Kwan
authors: YK
authors: Cheong
authors: Institute for Metabolic Disease, Wonkwang University School of Medicine, Iksan 570‑749, Republic of Korea.
authors: Seong Hoon
authors: SH
authors: Park
authors: Department of Biological Science, University of Ulsan, Ulsan 680‑749, Republic of Korea.
authors: Hun-Taeg
authors: HT
authors: Chung
authors: Department of Microbiology and Immunology, Wonkwang University School of Medicine, Iksan 570‑749, Republic of Korea.
authors: Hyun-Ock
authors: HO
authors: Pae
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008665:Metalloporphyrins / Q000494:pharmacology; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D016877:Oxidants / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D019308:Palmitic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011524:Protoporphyrins / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; C508600:IL6 protein, human; C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D015850:Interleukin-6; D008665:Metalloporphyrins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D016877:Oxidants; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; D013267:Stilbenes; D019308:Palmitic Acid; D009569:Nitric Oxide; C041525:3,3',4,5'-tetrahydroxystilbene; C032628:tin protoporphyrin IX; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D000077185:Resveratrol