Protection of vascular cells from oxidative stress by proteasome inhibition depends on Nrf2

Dreger, Henryk; Westphal, Kera; Wilck, Nicola; Baumann, Gert; Stangl, Verena; Stangl, Karl; Meiners, Silke

doi:10.1093/cvr/cvp279

Cited by 84 publications

(59 citation statements)

References 60 publications

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“…8D). These genes are the targets of the transcription factor Nrf2, which is activated under oxidative stress (37,50). Continuous activation of Nrf2 is closely related to the proliferation of cancer cells (51).…”

Section: Discussionmentioning

confidence: 99%

Disruption of the Sjögren-Larsson Syndrome Gene Aldh3a2 in Mice Increases Keratinocyte Growth and Retards Skin Barrier Recovery

Naganuma

Takagi

Kanetake

et al. 2016

Journal of Biological Chemistry

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The fatty aldehyde dehydrogenase (FALDH) ALDH3A2 is the causative gene of Sjögren Larsson syndrome (SLS Sjögren-Larsson syndrome (SLS)2 is a hereditary neurocutaneous disorder caused by mutations in the fatty aldehyde dehydrogenase (FALDH) gene, ALDH3A2. The major symptoms of SLS are mental retardation, spastic di-or tetraplegia, and ichthyosis, with crystalline macular dystrophy sometimes comorbid (1). ALDH3A2 catalyzes the conversion of fatty aldehydes with medium-chain (MC) to very-long-chain fatty acids (FA) (MC, C5-C10; long-chain (LC), C11-C20; and very-longchain, ՆC21), with the most preferred substrates being C16 and C18 aldehydes (2, 3). To date, more than 70 mutations have been found in the ALDH3A2 gene of SLS patients, and most of them cause Ͼ90% reduction in enzyme activity (4). Because aldehyde molecules are reactive and toxic in general, it is considered that accumulated fatty aldehydes cause the SLS pathology by reacting with certain important proteins in the nervous system and epidermis and compromising their functions. Furthermore, the literature lacks a detailed description of the characteristics of Aldh3a2 knock-out mice.The skin symptom ichthyosis is characterized by dry, thickened, and scaly skin, often likened to fish scales, and is caused by a skin permeability barrier defect related to multilayered lipids (lipid lamellae) in the epidermis. The epidermis is composed of four cell layers, the stratum basale, stratum spinosum, stratum granulosum, and the stratum corneum, the last of which is the site of these lipid lamellae, and accordingly has the most important role in skin barrier formation (5, 6). Keratinocytes proliferate in the stratum basale and migrate outward, differentiating into cell layer-specific cell types. The major lipid components of lipid lamellae are ceramides, cholesterol, and FAs, with ceramides being the most abundant (5, 6). A variety of ceramide species exist in the epidermis. Among them, acylceramides are a class of epidermis-specific ceramides that play an essential role in skin barrier formation (7,8). Ceramides are normally composed of a long-chain base (LCB) and a FA (9). However, acylceramides contain an additional hydrophobic chain (linoleic acid), which is esterified with the hydroxylated -carbon of the FA. In the epidermis of SLS patients, some ceramide species, including the acylceramide EOS (a combination of an esterified -hydroxy FA and the LCB sphingosine), are greatly reduced (10).Several metabolic pathways generate the substrates of ALDH3A2, fatty aldehydes. These include metabolic pathways of leukotriene B 4 , diet-derived phytol, plasmalogens, and fatty alcohols (11)(12)(13)(14)(15). Furthermore, we recently revealed that metabolism of LCBs also generates fatty aldehydes, i.e. hexadecanal (C16:0 aldehyde) from dihydrosphingosine (DHS) and

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Section: Discussionmentioning

confidence: 99%

Disruption of the Sjögren-Larsson Syndrome Gene Aldh3a2 in Mice Increases Keratinocyte Growth and Retards Skin Barrier Recovery

Naganuma

Takagi

Kanetake

et al. 2016

Journal of Biological Chemistry

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“…[8][9][10][11][12]21 One mechanism mediating the antioxidative effects of low-dose PI in cardiovascular cells is stabilization of oxidative stress-related transcription factor nuclear erythroid 2-related factor 2. 9,21 In line with these previous in vitro observations, we found definite antioxidative effects of low-dose bortezomib treatment in hypercholesterolemic LDLR−/− mice in the present study. Serum content of lipid peroxidation by guest on May 13, 2018 http://atvb.ahajournals.org/ products, which was markedly increased in hypercholesterolemic LDLR−/2 mice compared with control diet-fed LDLR−/− mice, was significantly decreased by bortezomib treatment.…”

Section: Discussionmentioning

confidence: 99%

“…[8][9][10][11][12] Moreover, low-dose PI was shown to enhance endothelial nitric oxide synthase expression and activity, improved endothelial function, 13 and prevented tumor necrosis factor--induced vascular dysfunction by reducing superoxide production and decreasing endothelin-1 levels in rat aortic rings. 14 We have recently shown that low-dose PI downregulates tumor necrosis factor--induced expression of VCAM-1 in endothelial cells and in a hypertensive rat model, which suggests that low-dose PI suppresses inflammatory cell adhesion in atherogenesis.…”

mentioning

confidence: 97%

Attenuation of Early Atherogenesis in Low-Density Lipoprotein Receptor–Deficient Mice by Proteasome Inhibition

Wilck

Fechner

Dreger

et al. 2012

ATVB

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Objective-Low and nontoxic proteasome inhibition has anti-inflammatory, antiproliferative, and antioxidative effects on vascular cells in vitro and in vivo. We hypothesized that low-dose inhibition of the proteasome could provide antiatherogenic protection. The present study investigated the effect of low-dose proteasome inhibition on early lesion formation in low-density lipoprotein receptor-deficient mice fed a Western-type diet. Methods and Results-Male low-density lipoprotein receptor-deficient mice, 10 weeks old, were fed a Western-type diet for 6 weeks with intraperitoneal injections of bortezomib or solvent. Bortezomib was injected at a dose of 50 mg/kg body weight. Cholesterol plasma levels were not affected by bortezomib treatment. En face Oil Red O staining of aortae and aortic root cryosections demonstrated significant reduction of atherosclerotic lesion coverage in bortezomib-treated animals. Bortezomib significantly reduced vascular cellular adhesion molecule-1 expression and macrophage infiltration as shown by histological analysis. Bortezomib treatment resulted in a significant reduction of superoxide content, lipid peroxidation and protein oxidation products, serum levels of monocyte chemoattractant protein-1, and interleukin-6. Gene expression microarray analysis showed that expressional changes induced by Western-type diet were attenuated by treatment with low-dose bortezomib. Conclusion-

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“…Oxidative stress stimulus can disrupt the Nrf2/Keap1 complex and induce the translocation of Nrf2 into the nucleus. Nrf2 then binds to ARE (antioxidant-response element), which eventually results in increased expression of antioxidant genes such as heme oxygenase-1 (HO-1) and glutathione synthetic enzyme to resist oxidative stress injury [19]. Our Western blot results indicated that the CB2 receptor activation induced an increase of Akt phosphorylation, Nrf2 nuclear translocation and HO-1 expression, accompanied by cardiac function improvement, fibrosis decrease and CPC activation.…”

Section: Discussionmentioning

confidence: 71%

“…The ELISA analysis revealed that MI led to significant increases in TNF-α and IL-6, as compared with those in the sham group (TNF-α: 19 …”

Section: Am1241 Treatment Decreased Mda Tnf-α and Il-6 Levels In Thementioning

confidence: 97%

Effects of cannabinoid receptor type 2 on endogenous myocardial regeneration by activating cardiac progenitor cells in mouse infarcted heart

Wang

et al. 2014

Sci. China Life Sci.

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Cannabinoid receptor type 2 (CB 2 ) activation is recently reported to promote proliferation of some types of resident stem cells (e.g., hematopoietic stem/progenitor cell or neural progenitor cell). Resident cardiac progenitor cell (CPC) activation and proliferation are crucial for endogenous cardiac regeneration and cardiac repair after myocardial infarction (MI). This study aims to explore the role and possible mechanisms of CB 2 receptor activation in enhancing myocardial repair. Our results revealed that CB 2 receptor agonist AM1241 can significantly increase CPCs by c-kit and Runx1 staining in ischemic myocardium as well as improve cardiomyocyte proliferation. AM1241 also decreased serum levels of MDA, TNF-α and IL-6 after MI. In addition, AM1241 can ameliorate left ventricular ejection fraction and fractional shortening, and reduce fibrosis. Moreover, AM1241 treatment markedly increased p-Akt and HO-1 expression, and promoted Nrf-2 nuclear translocation. However, PI3K inhibitor wortmannin eliminated these cardioprotective roles of AM1241. In conclusion, AM1241 could induce myocardial regeneration and improve cardiac function, which might be associated with PI3K/Akt/Nrf2 signaling pathway activation. Our findings may provide a promising strategy for cardiac endogenous regeneration after MI. CB 2 receptor, cardiac progenitor cells, endogenous cardiac regeneration Citation:Wang YB, Ma S, Wang Q, Hu WX, Wang DJ, Li XJ, Su T, Qin X, Zhang XT, Ma K, Chen JW, Xiong LZ, Cao F. Effects of cannabinoid receptor type 2 on endogenous myocardial regeneration by activating cardiac progenitor cells in mouse infarcted heart.

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Protection of vascular cells from oxidative stress by proteasome inhibition depends on Nrf2

Abstract: Nrf2-dependent transcriptional activation of antioxidative enzymes is crucial for proteasome inhibitor-mediated protection of vascular cells against oxidative stress.

Cited by 84 publications

References 60 publications

Disruption of the Sjögren-Larsson Syndrome Gene Aldh3a2 in Mice Increases Keratinocyte Growth and Retards Skin Barrier Recovery

Disruption of the Sjögren-Larsson Syndrome Gene Aldh3a2 in Mice Increases Keratinocyte Growth and Retards Skin Barrier Recovery

Attenuation of Early Atherogenesis in Low-Density Lipoprotein Receptor–Deficient Mice by Proteasome Inhibition

Effects of cannabinoid receptor type 2 on endogenous myocardial regeneration by activating cardiac progenitor cells in mouse infarcted heart

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