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Mol Med Rep. 2015 Jul;12(1):937-44. doi: 10.3892/mmr.2015.3553. Epub 2015 Mar 26.

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.

Author information

1
Department of Microbiology and Immunology, Wonkwang University School of Medicine, Iksan 570‑749, Republic of Korea.
2
Department of Anesthesiology and Pain Medicine, Wonkwang University School of Medicine, Iksan 570‑749, Republic of Korea.
3
Institute for Metabolic Disease, Wonkwang University School of Medicine, Iksan 570‑749, Republic of Korea.
4
Department of Biological Science, University of Ulsan, Ulsan 680‑749, Republic of Korea.

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.

PMID:
25815690
PMCID:
PMC4438933
DOI:
10.3892/mmr.2015.3553
[Indexed for MEDLINE]
Free PMC Article

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