High-selenium lentil diet protects against arsenic-induced atherosclerosis in a mouse model

Krohn, Regina M.; Lemaire, Maryse; Silva, Luis F. Negro; Lemarié, Catherine A.; Bolt, Alicia M.; Mann, Koren K.; Smits, Judit E. G.

doi:10.1016/j.jnutbio.2015.07.003

Cited by 57 publications

(36 citation statements)

References 43 publications

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“…The McGill Animal Care Committee is IACUC approved. For long-term arsenic exposure experiments, apoE -/- male mice (3 week old, n = 5 animals per group) were grouped with cage companionsand fed ad libitum with normal rodent chow (2018; Harlan Laboratories Inc., WI, USA)or deficient (0.009 mg/kg) or high (0.3 mg/kg) selenium-containing lentil diet (Krohn et al , [ 27 ] in press ) at the animal facility. The normal rodent chow contains 0.2 mg/kg selenium (2018; Harlan Laboratories).…”

Section: Methodsmentioning

confidence: 99%

Arsenic Exposure Increases Monocyte Adhesion to the Vascular Endothelium, a Pro-Atherogenic Mechanism

et al. 2015

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Epidemiological studies have shown that arsenic exposure increases atherosclerosis, but the mechanisms underlying this relationship are unknown. Monocytes, macrophages and platelets play an important role in the initiation of atherosclerosis. Circulating monocytes and macrophages bind to the activated vascular endothelium and migrate into the sub-endothelium, where they become lipid-laden foam cells. This process can be facilitated by platelets, which favour monocyte recruitment to the lesion. Thus, we assessed the effects of low-to-moderate arsenic exposure on monocyte adhesion to endothelial cells, platelet activation and platelet-monocyte interactions. We observed that arsenic induces human monocyte adhesion to endothelial cells in vitro. These findings were confirmed ex vivo using a murine organ culture system at concentrations as low as 10 ppb. We found that both cell types need to be exposed to arsenic to maximize monocyte adhesion to the endothelium. This adhesion process is specific to monocyte/endothelium interactions. Hence, no effect of arsenic on platelet activation or platelet/leukocyte interaction was observed. We found that arsenic increases adhesion of mononuclear cells via increased CD29 binding to VCAM-1, an adhesion molecule found on activated endothelial cells. Similar results were observed in vivo, where arsenic-exposed mice exhibit increased VCAM-1 expression on endothelial cells and increased CD29 on circulating monocytes. Interestingly, expression of adhesion molecules and increased binding can be inhibited by antioxidants in vitro and in vivo. Together, these data suggest that arsenic might enhance atherosclerosis by increasing monocyte adhesion to endothelial cells, a process that is inhibited by antioxidants.

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Section: Methodsmentioning

confidence: 99%

Arsenic Exposure Increases Monocyte Adhesion to the Vascular Endothelium, a Pro-Atherogenic Mechanism

et al. 2015

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“…Since PARP-1 and XPA are involved in DNA repair, this evidence strongly suggests that dietary Zn(II) supplementation may have potential utility as a chemopreventive intervention in vulnerable populations, to mitigate adverse health effects of low level As(III) exposure. It is worth noting that dietary selenium supplementation has also been proposed as another such potentially protective intervention to alleviate As(III) exposure, however, distinct mechanisms likely underlie the chemopreventive effects of Zn(II) and selenium [41-43]. …”

Section: Discussionmentioning

confidence: 99%

Kinetics and thermodynamics of zinc(II) and arsenic(III) binding to XPA and PARP-1 zinc finger peptides

Huestis

Zhou

Chen

et al. 2016

Journal of Inorganic Biochemistry

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Inhibition of DNA repair is an established mechanism of arsenic co-carcinogenesis, and may be perpetuated by the binding of As(III) to key zinc finger (zf) DNA repair proteins. Validated molecular targets of As(III) include the first zinc finger domain of Poly (ADP-Ribose) Polymerase 1 (PARP-1), and the zinc finger domain of Xeroderma Pigmentosum Complementation Group A (XPA). In order to gain an understanding of the thermodynamic and kinetic parameters of the interaction of As(III) with these two zinc finger motifs, a fluorescence based approach was used to investigate Zn(II) and As(III) binding to synthetic model peptides corresponding to the zf motif of XPA and first zf motif of PARP-1, referred to in this paper as XPAzf and PARP-1zf-1, respectively. While XPAzf and PARP-1zf-1 display similar relative affinities for As(III), PARP-1zf-1 shows a potential kinetic advantage over XPAzf for As(III) binding, with a rate constant for the fast phase of formation of As(III)-PARP-1zf-1 approximately 4-fold higher than for As(III)-XPAzf. However, the binding of Zn(II) with either peptide proceeds at a faster rate than As(III). Notably, XPAzf demonstrates comparable affinities for binding both metals, while PARP-1zf-1 shows a slightly higher affinity for Zn(II), suggesting that the relative concentrations of Zn(II) and As(III) in a system may significantly influence which species predominates in zinc finger occupancy. These results provide insight into the mechanisms underlying interactions between zinc finger structures and As(III), and highlight the potential utility of zinc supplementation in mitigating adverse effects of As(III) on zinc finger functions in vivo.

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“…Low selenium leads to decreased activity of antioxidant enzymes, resulting in the aggravation of atherosclerosis. Selenium supplements have significant therapeutic effects in patients with atherosclerosis ( 3 ). In addition, low selenium is a major cause of Keshan disease, which manifests with myocardial necrosis ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of selenium on myocardial apoptosis by modifying the activity of mitochondrial STAT3 and regulating potassium channel expression

Zhang

Deng

Lei

et al. 2017

Experimental and Therapeutic Medicine

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The present study investigated the effects of myocardial mitochondrial signal transduction and activator of transcription 3 (STAT3), succinate dehydrogenase activity and changes of potassium channel expression on cardiomyocyte apoptosis under low selenium conditions. Primary cultured cardiomyocytes from neonatal mice were divided into the non-toxic control group (0.1 µM sodium selenite) and low selenium treatment group (0.05 µM sodium selenite) according to different selenium concentrations. The expression of mitochondrial STAT3, p-STAT3, p-Kv1.2 potassium channel and apoptosis-related proteins, Bax and Bcl-2, were assessed by immunoblotting. Succinate dehydrogenase activity was measured by spectrophotometry. Flow cytometry was used to detect cardiomyocyte apoptosis. Low selenium treatment reduced the expression of p-STAT3, but did not affect the expression of STAT3. In addition, low selenium treatment reduced the activity of mitochondrial STAT3 and succinate dehydrogenase in cardiomyocytes, leading to injury of myocardial mitochondria. Compared with the control group, low selenium conditions reduced the activity of p-Kv1.2 and reduced the normal electrophysiological function of cardiomyocytes. In the low selenium-treated group, the expression of Bax protein increased, whereas the expression of Bcl-2 protein decreased. The apoptotic rate increased. In conclusion, selenium deficiency in cardiomyocytes leads to decreased potassium channel expression and decreased mitochondrial STAT3 activity and mitochondrial function, which in turn promotes the apoptosis of cardiomyocytes.

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High-selenium lentil diet protects against arsenic-induced atherosclerosis in a mouse model

Cited by 57 publications

References 43 publications

Arsenic Exposure Increases Monocyte Adhesion to the Vascular Endothelium, a Pro-Atherogenic Mechanism

Arsenic Exposure Increases Monocyte Adhesion to the Vascular Endothelium, a Pro-Atherogenic Mechanism

Kinetics and thermodynamics of zinc(II) and arsenic(III) binding to XPA and PARP-1 zinc finger peptides

Effects of selenium on myocardial apoptosis by modifying the activity of mitochondrial STAT3 and regulating potassium channel expression

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