Piceatannol attenuates homocysteine-induced endoplasmic reticulum stress and endothelial cell damage via heme oxygenase-1 expression
| Autor: | Hyun-Ock Pae, Jin-Sang Kil, Sun-Oh Jeong, Hun-Taeg Chung |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
NF-E2-Related Factor 2 Clinical Biochemistry Apoptosis Biology medicine.disease_cause Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Annexin Stilbenes medicine Humans Endoplasmic Reticulum Chaperone BiP Homocysteine Cells Cultured chemistry.chemical_classification Piceatannol Reactive oxygen species Endoplasmic reticulum Organic Chemistry Endothelial Cells Endoplasmic Reticulum Stress Molecular biology Heme oxygenase Oxidative Stress 030104 developmental biology chemistry 030220 oncology & carcinogenesis Unfolded protein response Reactive Oxygen Species Oxidative stress Heme Oxygenase-1 |
| Zdroj: | Amino acids. 49(4) |
| ISSN: | 1438-2199 |
| Popis: | A growing body of evidence implicates endoplasmic reticulum (ER)-induced cellular dysfunction and apoptosis as important factors to a variety of diseases. In endothelial cells (ECs), the sulfur-containing amino acid homocysteine (Hcy) causes EC apoptosis and reactive oxygen species (ROS) generation through induction of ER stress. Here, we have investigated whether piceatannol (Pic), a resveratrol analog, could protect ECs against Hcy-induced apoptosis, oxidative stress and ER stress, with specific emphasis on heme oxygenase-1 (HO-1). In human ECs, we determined the effects of Hcy and Pic on annexin V positivity, glucose-regulated protein 78 kDa (GRP78) and C/EBP homologous protein (CHOP) expression, X-box binding protein 1 (Xbp-1) mRNA slicing, and ROS-sensitive dihydroethidium (DHE) oxidation. Hcy increased annexin V-positive cells, DHE oxidation, GRP78 and CHOP expression and Xbp-1 mRNA splicing, indicating that Hcy induces apoptosis, oxidative stress and ER stress. Pretreatment of ECs with Pic significantly inhibited Hcy-induced apoptosis, ROS generation and ER stress. Pic also increased HO-1 expression via activation of nuclear factor-E2-related factor 2 (Nrf2). Interestingly, the inhibitory effects of Pic on Hcy-induced apoptosis, ROS generation and ER stress were abolished by down-regulation of HO-1 expression, while mimicked by treatment of ECs with the HO-1 inducer hemin. Overall, these results suggest that Pic may protect ECs against Hcy-induced apoptosis, oxidative stress and ER stress via Nrf2-dependent HO-1 expression. |
| Databáze: | OpenAIRE |
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