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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
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Autor/innen der Med Uni Graz:
Crnkovic Slaven
Frank Saša
Frisch Marie-Therese
Olschewski Andrea
Olschewski Horst
Sereinigg Michael
Stacher-Priehse Elvira
Stiegler Philipp
Stulnig Gabriel
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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
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