Protein Disulfide Isomerase Modification and Inhibition Contribute to ER Stress and Apoptosis Induced by Oxidized Low Density Lipoproteins

Muller, C.; Bandemer, Jan; Vindis, Cécile; Camaré, Caroline; Mucher, Elodie; Guéraud, Françoise; Larroque-Cardoso, Pauline; Bernis, Corinne; Augé, Nathalie; Salvayre, Robert; Negre-Salvayre, Anne

doi:10.1089/ars.2012.4577

Cited by 76 publications

(66 citation statements)

References 49 publications

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“…Mechanisms orchestrating this response deserve further investigation and may relate, at least in part, to the severe ER stress during vessel repair because sustained ER stress is often associated with increased PDI expression in several diseases, 12 including atherosclerosis. 28 Our data ( Figure 2) as well as recent studies from our group (T. Araujo et al, unpublished data, 2015) suggest that pecPDI levels directly correlate with total PDI expression. This is consistent with the correlations between total PDI and vessel remodeling observed in human specimens (Figure 1).…”

Section: Discussionsupporting

confidence: 83%

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Peri/Epicellular Protein Disulfide Isomerase Sustains Vascular Lumen Caliber Through an Anticonstrictive Remodeling Effect

et al. 2016

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V ascular remodeling involves changes for the whole-vessel circumference and crucially determines lumen caliber 1 in physio(patho)logical situations, such as shear-stress responses, restenosis postangioplasty, 1-3 or native atherosclerosis. 1,4 Moreover, cellular mechanisms governing conductance vessel remodeling are likely shared by small-vessel remodeling, for example, in hypertension.5 Despite such relevance, mechanisms of vessel remodeling are not well known. The identification of endothelium 6 and nitric oxide 7 dependency of shear-induced remodeling raised possible mediator roles of redox processes, as indeed supported by many subsequent studies. 3,8 We showed previously that superoxide dismutase underactivity favors constrictive remodeling after injury (AI), whereas exogenous replenishment of SOD3(ecSOD) rescued bioactive nitric oxide from inducible NO synthase and normalized vessel caliber by counteracting constrictive remodeling rather than neointimal growth. 3 The randomized clinical trial Multivitamins and Probucol Study showed that the antioxidant probucol significantly prevented restenosis postballoon angioplasty, essentially by preventing constrictive remodeling rather than neointima formation. 9Such redox-responsiveness is in line with the importance of redox pathways in cytoskeletal dynamics 10 and extracellular matrix organization, 11 which are both crucially involved in vessel remodeling. However, molecular determinants of such redox signaling pathways remain unclear.Abstract-Whole-vessel remodeling critically determines lumen caliber in vascular (patho)physiology, and it is reportedly redox-dependent. We hypothesized that the cell-surface pool of the endoplasmic reticulum redox chaperone protein disulfide isomerase-A1 (peri/epicellular=pecPDI), which is known to support thrombosis, also regulates disease-associated vascular architecture. In human coronary atheromas, PDI expression inversely correlated with constrictive remodeling and plaque stability. In a rabbit iliac artery overdistension model, there was unusually high PDI upregulation (≈25-fold versus basal, 14 days postinjury), involving both intracellular and pecPDI. PecPDI neutralization with distinct anti-PDI antibodies did not enhance endoplasmic reticulum stress or apoptosis. In vivo pecPDI neutralization with PDI antibodycontaining perivascular gel from days 12 to 14 post injury promoted 25% decrease in the maximally dilated arteriographic vascular caliber. There was corresponding whole-vessel circumference loss using optical coherence tomography without change in neointima, which indicates constrictive remodeling. This was accompanied by decreased hydrogen peroxide generation. Constrictive remodeling was corroborated by marked changes in collagen organization, that is, switching from circumferential to radial fiber orientation and to a more rigid fiber type. The cytoskeleton architecture was also disrupted; there was a loss of stress fiber coherent organization and a switch from thin to medium thickness actin fibers, all leading to...

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Section: Discussionsupporting

confidence: 83%

“…Previously reported vasculoprotective effects of PDI focused mainly on prosurvival intracellular PDI effects in ER dysfunction associated with oxidized lipids 28 and hypoxia. 29 Our data add to other specific effects of pecPDI pool, which include immune reactions, 16 pathogen response, 16,27 and thrombosis.…”

Section: Discussionmentioning

confidence: 99%

Peri/Epicellular Protein Disulfide Isomerase Sustains Vascular Lumen Caliber Through an Anticonstrictive Remodeling Effect

et al. 2016

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“…109 These adducted proteins directly affect ER function, especially protein disulfide isomerase. 110 In support of this idea, it was shown that the folding of protein to allow optimal formation of disulfide bonds is highly redox-dependent in the ER. 111 Thus, the accumulation of misfolded proteins with HNE-adducts in ER could compromise cell survival.…”

Section: Hne: a Serial Killermentioning

confidence: 96%

Cell death and diseases related to oxidative stress:4-hydroxynonenal (HNE) in the balance

et al. 2013

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During the last three decades, 4-hydroxy-2-nonenal (HNE), a major a,b-unsaturated aldehyde product of n-6 fatty acid oxidation, has been shown to be involved in a great number of pathologies such as metabolic diseases, neurodegenerative diseases and cancers. These multiple pathologies can be explained by the fact that HNE is a potent modulator of numerous cell processes such as oxidative stress signaling, cell proliferation, transformation or cell death. The main objective of this review is to focus on the different aspects of HNE-induced cell death, with a particular emphasis on apoptosis. HNE is a special apoptotic inducer because of its abilities to form protein adducts and to propagate oxidative stress. It can stimulate intrinsic and extrinsic apoptotic pathways and interact with typical actors such as tumor protein 53, JNK, Fas or mitochondrial regulators. At the same time, due to its oxidant status, it can also induce some cellular defense mechanisms against oxidative stress, thus being involved in its own detoxification. These processes in turn limit the apoptotic potential of HNE. These dualities can imbalance cell fate, either toward cell death or toward survival, depending on the cell type, the metabolic state and the ability to detoxify.

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“…Loss of PDIs activity has been associated with the pathogenesis of numerous disease states (6). In particular, PDI and PDIA3 prevent apoptotic cell death associated with ER stress and protein misfolding in various in vivo and in vitro models (7)(8)(9)(10)(11)(12)(13). The up-regulation of PDIA3 correlates with the accumulation of misfolded prion proteins and suppresses prion neurotoxicity (7), whereas reducing PDIA3 expression in cancer cells increases the apoptotic response to fenretinide (12).…”

Section: Protein Disulfide Isomerase (Pdi)mentioning

confidence: 99%

Proapoptotic Activities of Protein Disulfide Isomerase (PDI) and PDIA3 Protein, a Role of the Bcl-2 Protein Bak

Zhao

Han

2015

Journal of Biological Chemistry

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Background: Protein disulfide isomerase (PDI) family members are chaperones involved in apoptotic signaling through unclear mechanisms. Results: Pharmacological inhibition of PDI and PDIA3 activities reduces apoptotic signaling. Purified PDI and PDIA3 proteins induce Bak-dependent mitochondrial outer membrane permeabilization in vitro. Conclusion: PDI and PDIA3 possess proapoptotic function through inducing Bak oligomerization. Significance: The data show a novel mechanism of PDI/PDIA3-mediated apoptosis.

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Protein Disulfide Isomerase Modification and Inhibition Contribute to ER Stress and Apoptosis Induced by Oxidized Low Density Lipoproteins

Cited by 76 publications

References 49 publications

Peri/Epicellular Protein Disulfide Isomerase Sustains Vascular Lumen Caliber Through an Anticonstrictive Remodeling Effect

Peri/Epicellular Protein Disulfide Isomerase Sustains Vascular Lumen Caliber Through an Anticonstrictive Remodeling Effect

Cell death and diseases related to oxidative stress:4-hydroxynonenal (HNE) in the balance

Proapoptotic Activities of Protein Disulfide Isomerase (PDI) and PDIA3 Protein, a Role of the Bcl-2 Protein Bak

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