The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
NAD(P)H Oxidase Nox-4 Mediates 7-Ketocholesterol-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Aortic Smooth Muscle Cells
Open accessAbstract
The mechanisms involved in the cytotoxic action of oxysterols in the pathogenesis of atherosclerosis still remain poorly understood. Among the major oxysterols present in oxidized low-density lipoprotein, we show here that 7-ketocholesterol (7-Kchol) induces oxidative stress and/or apoptotic events in human aortic smooth muscle cells (SMCs). This specific effect of 7-Kchol is mediated by a robust upregulation (threefold from the basal level) of Nox-4, a reactive oxygen species (ROS)-generating NAD(P)H oxidase homologue. This effect was highlighted by silencing Nox-4 expression with a specific small interfering RNA, which significantly reduced the 7-Kchol-induced production of ROS and abolished apoptotic events. Furthermore, the 7-Kchol activating pathway included an early triggering of endoplasmic reticulum stress, as assessed by transient intracellular Ca(2+) oscillations, and the induction of the expression of the cell death effector CHOP and of GRP78/Bip chaperone via the activation of IRE-1, all hallmarks of the unfolded protein response (UPR). We also showed that 7-Kchol activated the IRE-1/Jun-NH(2)-terminal kinase (JNK)/AP-1 signaling pathway to promote Nox-4 expression. Silencing of IRE-1 and JNK inhibition downregulated Nox-4 expression and subsequently prevented the UPR-dependent cell death induced by 7-Kchol. These findings demonstrate that Nox-4 plays a key role in 7-Kchol-induced SMC death, which is consistent with the hypothesis that Nox-4/oxysterols are involved in the pathogenesis of atherosclerosis.
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Cites
Proapoptotic BAX and BAK: A Requisite Gateway to Mitochondrial Dysfunction and Death
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NAD(P)H Oxidase: Role in Cardiovascular Biology and Disease
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Reactive Oxygen Species in Metabolic and Inflammatory Signaling
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Autophagy Is Activated for Cell Survival after Endoplasmic ReticulumStress
Ogata, M., Hino, S.-I., Saito, A., Morikawa, K., Kondo, S., Kanemoto, S., Murakami, T., Taniguchi, M., Tanii, I., Yoshinaga, K., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.01453-06 · Cited by 1,832
Endoplasmic Reticulum Stress and Oxidative Stress in Cell Fate Decision and Human Disease
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Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets
Drummond, G. R., Selemidis, S., Griendling, K. K., & Sobey, C. G. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3403 · Cited by 899
Metadata
- Authors
- Pedruzzi, E., Guichard, C., Ollivier, V., Driss, F., Fay, M., Prunet, C., Marie, J.-C., Pouzet, C., Samadi, M., Elbim, C., O'Dowd, Y., Bens, M., Vandewalle, A., Gougerot-Pocidalo, M.-A., Lizard, G., & Ogier-Denis, E.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2004-12-01
- Volume
- 24
- Issue
- 24
- Pages
- 10703-10717
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2150277507
- Cited by
- 435
- References
- 58
- FWCI
- 9.12
- Type
- journal article
- Language
- en
- Open access
- green
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- The paper
- Pedruzzi, E., Guichard, C., Ollivier, V., Driss, F., Fay, M., Prunet, C., Marie, J.-C., Pouzet, C., Samadi, M., Elbim, C., O'Dowd, Y., Bens, M., Vandewalle, A., Gougerot-Pocidalo, M.-A., Lizard, G., & Ogier-Denis, E. (2004). NAD(P)H Oxidase Nox-4 Mediates 7-Ketocholesterol-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Aortic Smooth Muscle Cells. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.24.24.10703-10717.2004
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
