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SHR Neuro Cancer Cardio Lipid Metab Microb
Stulnig, G; Frisch, MT; Crnkovic, S; Stiegler, P; Sereinigg, M; Stacher, E; Olschewski, H; Olschewski, A; Frank, S.
Docosahexaenoic acid (DHA)-induced heme oxygenase-1 attenuates cytotoxic effects of DHA in vascular smooth muscle cells.
Atherosclerosis. 2013; 230(2):406-413
Doi: 10.1016/j.atherosclerosis.2013.08.002
Web of Science
PubMed
FullText
FullText_MUG
- Leading authors Med Uni Graz
- Frank Sasa
- Melcher Marie-Therese
- Stulnig Gabriel
- Co-authors Med Uni Graz
- Crnkovic Slaven
- Olschewski Andrea
- Olschewski Horst
- Sereinigg Michael
- Stacher-Priehse Elvira
- Stiegler Philipp
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- Abstract:
- Docosahexaenoic acid (DHA), a member of n-3 polyunsaturated fatty acids (n-3 PUFA) is a potent regulator of molecular events implicated in cardiovascular health. In a previous study we found that Ca(2+)-dependent oxidative stress is the central and initial event responsible for induction of unfolded protein response (UPR), cell cycle arrest and apoptosis in DHA treated primary human smooth muscle cells isolated from small pulmonary artery (hPASMC). In the present study we examined the impact of heme oxygenase (HO)-1, induced by DHA, on DHA-induced oxidative stress, UPR, cell proliferation and apoptosis in hPASMC. DHA led to a time- and concentration-dependent increase in HO-1 mRNA and protein levels in hPASMC. The DHA-induced HO-1 upregulation could be attenuated by preincubation of cells with a strong antioxidant Tempol or by siRNA-mediated depletion of nuclear factor erythroid 2-related factor-2 (Nrf2). In DHA-treated hPASMC, depletion of HO-1 by siRNA-mediated silencing resulted in increased levels of reactive oxygen species (ROS) and increased duration of UPR, the latter revealed by monitoring of spliced X-box binding protein 1 (XBP-1) variant. Moreover, HO-1 silencing augmented apoptosis in DHA-treated hPASMC as found by increased numbers of cleaved caspase-3-positive cells. HO-1 silencing did not affect proliferation of hPASMC exposed to DHA. Our results indicate that DHA-induced, ROS-dependent upregulation of HO-1 attenuates oxidative stress, UPR and apoptosis in DHA-treated hPASMC. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Antioxidants - chemistry
- Apoptosis -
- Caspase 3 - metabolism
- Cell Proliferation -
- Cell Survival -
- Cyclic N-Oxides - chemistry
- DNA-Binding Proteins - genetics
- DNA-Binding Proteins - metabolism
- Docosahexaenoic Acids - metabolism
- Dose-Response Relationship, Drug -
- Gene Expression Regulation, Enzymologic -
- Gene Silencing -
- Heme Oxygenase-1 - metabolism
- Humans -
- Muscle, Smooth, Vascular - drug effects
- Muscle, Smooth, Vascular - metabolism
- NF-E2-Related Factor 2 - metabolism
- Oxidative Stress -
- Pulmonary Artery - drug effects
- Pulmonary Artery - metabolism
- RNA, Small Interfering - metabolism
- Reactive Oxygen Species - metabolism
- Regulatory Factor X Transcription Factors -
- Spin Labels -
- Time Factors -
- Transcription Factors - genetics
- Transcription Factors - metabolism
- Unfolded Protein Response -
- X-Box Binding Protein 1 -
- Find related publications in this database (Keywords)
- ROS
- Apoptosis
- UPR
- DHA
- HO-1