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Arsenic augments the uptake of oxidized LDL by upregulating the expression of lectin-like oxidized LDL receptor in mouse aortic endothelial cells.
Toxicol Appl Pharmacol. 2013 Dec 15; 273(3):651-8.TA

Abstract

Although chronic arsenic exposure is a well-known risk factor for cardiovascular diseases, including atherosclerosis, the molecular mechanism underlying arsenic-induced atherosclerosis remains obscure. Therefore, this study aimed to elucidate this molecular mechanism. We examined changes in the mRNA level of the lectin-like oxidized LDL (oxLDL) receptor (LOX-1) in a mouse aortic endothelial cell line, END-D, after sodium arsenite (SA) treatment. SA treatment significantly upregulated LOX-1 mRNA expression; this finding was also verified at the protein expression level. Flow cytometry and fluorescence microscopy analyses showed that the cellular uptake of fluorescence (Dil)-labeled oxLDL was significantly augmented with SA treatment. In addition, an anti-LOX-1 antibody completely abrogated the augmented uptake of Dil-oxLDL. We observed that SA increased the levels of the phosphorylated forms of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB)/p65. SA-induced upregulation of LOX-1 protein expression was clearly prevented by treatment with an antioxidant, N-acetylcysteine (NAC), or an NF-κB inhibitor, caffeic acid phenethylester (CAPE). Furthermore, SA-augmented uptake of Dil-oxLDL was also prevented by treatment with NAC or CAPE. Taken together, our results indicate that arsenic upregulates LOX-1 expression through the reactive oxygen species-mediated NF-κB signaling pathway, followed by augmented cellular oxLDL uptake, thus highlighting a critical role of the aberrant LOX-1 signaling pathway in the pathogenesis of arsenic-induced atherosclerosis.

Authors+Show Affiliations

Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24145059

Citation

Hossain, Ekhtear, et al. "Arsenic Augments the Uptake of Oxidized LDL By Upregulating the Expression of Lectin-like Oxidized LDL Receptor in Mouse Aortic Endothelial Cells." Toxicology and Applied Pharmacology, vol. 273, no. 3, 2013, pp. 651-8.
Hossain E, Ota A, Karnan S, et al. Arsenic augments the uptake of oxidized LDL by upregulating the expression of lectin-like oxidized LDL receptor in mouse aortic endothelial cells. Toxicol Appl Pharmacol. 2013;273(3):651-8.
Hossain, E., Ota, A., Karnan, S., Damdindorj, L., Takahashi, M., Konishi, Y., Konishi, H., & Hosokawa, Y. (2013). Arsenic augments the uptake of oxidized LDL by upregulating the expression of lectin-like oxidized LDL receptor in mouse aortic endothelial cells. Toxicology and Applied Pharmacology, 273(3), 651-8. https://doi.org/10.1016/j.taap.2013.10.012
Hossain E, et al. Arsenic Augments the Uptake of Oxidized LDL By Upregulating the Expression of Lectin-like Oxidized LDL Receptor in Mouse Aortic Endothelial Cells. Toxicol Appl Pharmacol. 2013 Dec 15;273(3):651-8. PubMed PMID: 24145059.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Arsenic augments the uptake of oxidized LDL by upregulating the expression of lectin-like oxidized LDL receptor in mouse aortic endothelial cells. AU - Hossain,Ekhtear, AU - Ota,Akinobu, AU - Karnan,Sivasundaram, AU - Damdindorj,Lkhagvasuren, AU - Takahashi,Miyuki, AU - Konishi,Yuko, AU - Konishi,Hiroyuki, AU - Hosokawa,Yoshitaka, Y1 - 2013/10/19/ PY - 2013/07/08/received PY - 2013/09/25/revised PY - 2013/10/04/accepted PY - 2013/10/23/entrez PY - 2013/10/23/pubmed PY - 2014/2/11/medline KW - 1,1′-Dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate KW - 2,7-dichlorofluorescin diacetate KW - 4′,6-diamidine-2′-phenylindole dihydrochloride KW - ABCA1 KW - AP-1 KW - ATP-binding cassette sub-family A member 1 KW - Arsenic exposure KW - Atherosclerosis KW - C-Jun N-terminal kinases KW - CAPE KW - DAPI KW - DCFH-DA KW - Dil KW - ECs KW - Erk1/2 KW - FACS KW - GAPDH KW - ICAM-1 KW - JNK KW - LOX-1 KW - LXR KW - MAPK KW - Molecular biology KW - N-acetylcysteine KW - NAC KW - NF-κB KW - ROS KW - Reactive oxygen species (ROS) KW - SA KW - SR-A KW - VCAM-1 KW - VSMCS KW - activator protein 1 KW - caffeic acid phenethylester KW - eNOS KW - endothelial cells KW - endothelial nitric oxide synthetase KW - extracellular signal-regulated protein kinases 1 and 2 KW - fluorescence-activated cell sorting KW - glyceraldehyde-3-phosphate dehydrogenase KW - intercellular adhesion molecule 1 KW - lectin-like oxidized low-density lipoprotein receptor KW - liver X receptor KW - mitogen-activated protein kinase KW - nuclear factor of kappa light polypeptide gene enhancer in B cells KW - oxLDL KW - oxidized low-density lipoprotein KW - reactive oxygen species KW - scavenger receptor A KW - sodium arsenite KW - vascular cell adhesion molecule KW - vascular smooth muscle cells SP - 651 EP - 8 JF - Toxicology and applied pharmacology JO - Toxicol Appl Pharmacol VL - 273 IS - 3 N2 - Although chronic arsenic exposure is a well-known risk factor for cardiovascular diseases, including atherosclerosis, the molecular mechanism underlying arsenic-induced atherosclerosis remains obscure. Therefore, this study aimed to elucidate this molecular mechanism. We examined changes in the mRNA level of the lectin-like oxidized LDL (oxLDL) receptor (LOX-1) in a mouse aortic endothelial cell line, END-D, after sodium arsenite (SA) treatment. SA treatment significantly upregulated LOX-1 mRNA expression; this finding was also verified at the protein expression level. Flow cytometry and fluorescence microscopy analyses showed that the cellular uptake of fluorescence (Dil)-labeled oxLDL was significantly augmented with SA treatment. In addition, an anti-LOX-1 antibody completely abrogated the augmented uptake of Dil-oxLDL. We observed that SA increased the levels of the phosphorylated forms of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB)/p65. SA-induced upregulation of LOX-1 protein expression was clearly prevented by treatment with an antioxidant, N-acetylcysteine (NAC), or an NF-κB inhibitor, caffeic acid phenethylester (CAPE). Furthermore, SA-augmented uptake of Dil-oxLDL was also prevented by treatment with NAC or CAPE. Taken together, our results indicate that arsenic upregulates LOX-1 expression through the reactive oxygen species-mediated NF-κB signaling pathway, followed by augmented cellular oxLDL uptake, thus highlighting a critical role of the aberrant LOX-1 signaling pathway in the pathogenesis of arsenic-induced atherosclerosis. SN - 1096-0333 UR - https://www.unboundmedicine.com/medline/citation/24145059/Arsenic_augments_the_uptake_of_oxidized_LDL_by_upregulating_the_expression_of_lectin_like_oxidized_LDL_receptor_in_mouse_aortic_endothelial_cells_ DB - PRIME DP - Unbound Medicine ER -