Iron nanoparticles increase 7-ketocholesterol-induced cell death, inflammation, and oxidation on murine cardiac HL1-NB cells

Kahn, Edmond; Baarine, Mauhamad; Pelloux, Sophie; Riedinger, Jean-Marc; Frouin, Frédérique; Tourneur, Yves; Lizard, Gérard

doi:10.2147/ijn.s8458

Cited by 31 publications

(19 citation statements)

References 45 publications

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“…These findings indicated that increased tissue iron stores are sufficient to increase serum ferritin and decrease serum adiponectin levels. Iron-loading induced oxidative stress with the overexpression of proinflammatory molecules, such as IL-6, MCP-1, TNF-a, and ICAM-1, in heart or blood vasculature (Kahn et al, 2010), which leads to endothelial and cardiac dysfunction. Therefore, it is plausible that decreased levels of adiponectin could be a risk index in cardiac inflammation and associated endothelial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Adiponectin Ameliorates Iron-Overload Cardiomyopathy through the PPARα–PGC-1–Dependent Signaling Pathway

Lin

Lian

Chen

et al. 2013

Molecular Pharmacology

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Adiponectin is a circulating adipose-derived cytokine that may act as an antioxidative and anti-inflammatory protein. Although adiponectin has been reported to exert cytoprotective effects in acute cardiac diseases, its effects on chronic heart failure are less clear. Therefore, we aimed to investigate whether adiponectin would have a beneficial effect in iron-induced chronic heart failure and to elucidate its regulation in cardiomyocytes. Mice were first treated with iron dextran for 4 weeks to induce iron-overload cardiomyopathy. They exhibited decreased survival with impaired left ventricle contractility and decreased serum adiponectin levels. In vivo cardiac adiponectin gene (ADIPOQ) overexpression with adenoassociated virus (AAV)-ADIPOQ ameliorated cardiac iron deposition and restored cardiac function in iron-overloaded mice. In addition, AAV-ADIPOQ-treated iron-overload mice had lower expression of inflammatory markers, including myeloperoxidase activity, monocyte chemotactic protein-1, tumor necrosis factor-a, interleukin-6, and intercellular adhesion molecule-1, than iron-overloaded mice not treated with AAV-ADIPOQ. Our in vitro study showed that adiponectin induced heme oxygenase-1 (HO-1) expression through the peroxisome proliferator-activated receptor (PPAR)a-HO-1 signaling pathway. Furthermore, the adiponectin-mediated beneficial effects were PPARa-dependent as the adiponectinmediated attenuation of iron deposition was abolished in PPARa-knockout mice. Finally, PPARa-HO-1 signaling involved PPARa and peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) binding and nuclear translocation, and their levels were increased by adiponectin therapy. Together, these findings suggest that adiponectin acts as an antiinflammatory signaling molecule and induces the expression of HO-1 through the PPARa-PGC-1 complex-dependent pathway in cardiomyocytes, resulting in the attenuation of iron-induced cardiomyopathy. Using adiponectin for adjuvant therapies in iron-overload cardiac dysfunction may be an option in the future.

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Section: Discussionmentioning

confidence: 99%

Adiponectin Ameliorates Iron-Overload Cardiomyopathy through the PPARα–PGC-1–Dependent Signaling Pathway

Lin

Lian

Chen

et al. 2013

Molecular Pharmacology

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“…10 To provide a biological specimen, a product combining Fe nanoparticles and Texas Red (MRC 98145; Institute für Diagnostik Forschung, Berlin, Germany) was injected into the vein of the tail of Balb/c female mice (10-13 weeks). 9 The concentration of the injected product was similar to that used for clinical purposes in humans (0.05 mM/kg).…”

Section: Materials and Methods Specimensmentioning

confidence: 99%

“…An algorithmic description of FAMIS is provided in a previous publication. 16 This presentation is an adaptation of a published figure reprinted from International Journal of Nanomedicine, 5, Kahn E, Baarine M, Pelloux S, et al Iron nanoparticles increase 7-ketocholesterol-induced cell death, inflammation, and oxidation on murine cardiac HL1-NB cells, 185-195, copyright (2010), with permission from Dove Medical Press Ltd. 10 It mentions excitation profiles, and images and factor curves are different. Abbreviation: FAMIS, factor analysis of medical image sequences.…”

Section: Image Analysismentioning

confidence: 99%

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Fluorescence excitation analysis by two-photon confocal laser scanning microscopy: a new method to identify fluorescent nanoparticles on histological tissue sections

Kahn

Tissot²,

Frère³

et al. 2012

IJN

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Abstract:In the present study, we make use of the ability of two-photon confocal laser scanning microscopes (CLSMs) equipped with tunable lasers to produce spectral excitation image sequences. Furthermore, unmixing, which is usually performed on emission image sequences, is performed on these excitation image sequences. We use factor analysis of medical image sequences (FAMIS), which produces factor images, to unmix spectral image sequences of stained structures in tissue sections to provide images of characterized stained cellular structures. This new approach is applied to histological tissue sections of mouse aorta containing labeled iron nanoparticles stained with Texas Red and counterstained with SYTO13, to obtain visual information about the accumulation of these nanoparticles in the arterial wall. The possible presence of Texas Red is determined using a two-photon CLSM associated with FAMIS via the excitation spectra. Texas Red and SYTO13 are thus differentiated, and corresponding factor images specify their possible presence and cellular localization. In conclusion, the designed protocol shows that sequences of images obtained by excitation in a two-photon CLSM enables characterization of Texas Red-stained nanoparticles and other markers. This methodology offers an alternative and complementary solution to the conventional use of emission spectra unmixing to localize fluorescent nanoparticles in tissue samples.

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“…In summary, only IL-8, hBD-1, and TIMP-2 showed a statistically significant difference in the mean concentration level; however, all biochemical indicators showed higher levels in control than in thermally stressed EVPOMEs. In addition, we evaluated the release of lactate dehydrogenase (LDH) into medium as an indicator of cell death (Kahn et al 2010). However, LDH was at undetectable levels despite our best efforts.…”

Section: Elisa Analysis Of Il-8 Hbd-1 Vegf Timp-1 and Timp-2 Frommentioning

confidence: 99%

Biochemical Indicators of Implantation Success of Tissue-Engineered Oral Mucosa

et al. 2014

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Real-time (RT) determination of the health of in vitro tissue-engineered constructs prior to grafting is essential for prediction of success of the implanted tissue-engineered graft. In addition, the US Food and Drug Administration requires specific release criteria in RT prior to the release of tissue-engineered devices for human use. In principle, assessing the viability and functionality of the cellular component can be achieved by quantifying the secretion of growth factors and chemokines of tissue-engineered constructs. Ex vivo-produced oral mucosa equivalents (EVPOMEs) were fabricated under thermally stressed conditions at 43 °C for 24 h to create a functionally compromised EVPOME. We used microchannel enzyme-linked immunosorbent assay to evaluate the functionality of the cellular component, oral keratinocytes, of stressed and unstressed EVPOMEs by measuring the release of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), human β-defensin 1 (hBD-1), and tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1 and -2) into the spent medium, which was collected on the same day prior to graft implantation into severe combined immunodeficiency mice. Implanted EVPOMEs' histology on the seventh postimplantation day was used to correlate outcomes of grafting to secreted amounts of IL-8, hBD-1, VEGF, TIMP-1, and TIMP-2 from corresponding EVPOMEs. Our findings showed that significantly higher levels of IL-8, hBD-1, and TIMP-2 were secreted from controls than from thermally stressed EVPOMEs. We also found a direct correlation between secreted VEGF and IL-8 and blood vessel counts of implanted EVPOMEs. We concluded that measuring the constitutive release of these factors can be used as noninvasive predictors of healthy tissue-engineered EVPOMEs in RT, prior to their implantation.

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Iron nanoparticles increase 7-ketocholesterol-induced cell death, inflammation, and oxidation on murine cardiac HL1-NB cells

Cited by 31 publications

References 45 publications

Adiponectin Ameliorates Iron-Overload Cardiomyopathy through the PPARα–PGC-1–Dependent Signaling Pathway

Adiponectin Ameliorates Iron-Overload Cardiomyopathy through the PPARα–PGC-1–Dependent Signaling Pathway

Fluorescence excitation analysis by two-photon confocal laser scanning microscopy: a new method to identify fluorescent nanoparticles on histological tissue sections

Biochemical Indicators of Implantation Success of Tissue-Engineered Oral Mucosa

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