Arsenite induces endothelial cytotoxicity by down-regulation of vascular endothelial nitric oxide synthase

Tsou, Tsui‐Chun; Tsai, Feng-Yuan; Hsieh, Yao-Wen; Li, Lih-Ann; Yeh, Szu Ching; Chang, Louis W.

doi:10.1016/j.taap.2005.03.001

Cited by 59 publications

(26 citation statements)

References 40 publications

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“…According to Tsou et al [21], eNOS from porcine aortic endothelial cells presents a dose-and timedependent decrease of activity and expression in presence of arsenite in the micromolar range. They proposed that arsenite decreases NO production by increasing eNOS degradation through the ubitiquinproteasome pathway and also through direct inhibition of eNOS activity, and the recent report by Kamada and collaborators [42] contributes to our understanding of NOS depletion associated with arsenic exposure.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the involvement of nitric oxide (NO) in arsenic toxicity has raised considerable interest, and it is the subject of numerous current studies in humans [17,18], animal models [19,20] and in vitro preparations [21]. Furthermore, nitrergic dysfunction can also be linked to oxidative stress, since inadequate levels of tetrahydrobiopterin, one of the cofactors for NO synthesis are thought to contribute to superoxide formation by nitric oxide synthase (NOS) [22,23].…”

Section: Introductionmentioning

confidence: 99%

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Decreased Nitric Oxide Production in the Rat Brain after Chronic Arsenic Exposure

et al. 2006

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Chronic arsenic exposure is associated with nervous system damage, vascular disease, hepatic and renal damage as well as different types of cancer. Alterations of nitric oxide (NO) in the periphery have been detected after arsenic exposure, and we explored here NO production in the brain. Female Wistar rats were exposed to arsenite in drinking water (4-5 mg/kg/day) from gestation, lactation and until 4 months of age. NOS activity, NO metabolites content, reactive oxygen species production (ROS) and lipid peroxidation (LPx) were determined in vitro in the striatum, and NO production was estimated in vivo measuring citrulline by microdialysis. Exposed animals showed a significantly lower response to NMDA receptor stimulation, reduction of NOS activity and decreased levels of nitrites and nitrates in striatum. These markers of NO function were accompanied by significantly higher levels of LPx and ROS production. These results provide evidence of NO dysfunction in the rat brain associated with arsenic exposure.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Decreased Nitric Oxide Production in the Rat Brain after Chronic Arsenic Exposure

et al. 2006

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“…In addition to the direct action of ROS on NO, As inhibits endothelial NO synthetasis (eNOS) (Fig. 1) (Lee et al 2003;Tsou et al 2005;Li et al 2007), it depletes GSH -one of the main antioxidant ROS scavengers -and inhibits redox enzymes (catalase, glutathione peroxidase and reductase, thioredoxin reductase, superoxide dysmutase). The disruption of antioxidant defense mechanisms and the blocking of new NO formation further decrease NO bioavailability and increase endothelial dysfunction (Pi et al 2000).…”

Section: Endothelial Dysfunction: the Link Between As And CV Disease?mentioning

confidence: 99%

Cardiovascular effects of arsenic: clinical and epidemiological findings

Stea

Bianchi

Cori

et al. 2013

Environ Sci Pollut Res

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“…VE-cadherin can be degraded through several signal pathways, such as proteasome, caspase, matrix metalloproteinase (MMP), and lysosome proteases (24)(25)(26)(27). To determine which pathway might be involved, the effect of different inhibitors was compared.…”

Section: Overexpression Of Spliced Xbp1 Induces Ec Apoptosis Through mentioning

confidence: 99%

Sustained activation of XBP1 splicing leads to endothelial apoptosis and atherosclerosis development in response to disturbed flow

Zeng

Zampetaki

Margariti

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

196

184

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X-box binding protein 1 (XBP1) is a key signal transducer in endoplasmic reticulum stress response, and its potential role in the atherosclerosis development is unknown. This study aims to explore the impact of XBP1 on maintaining endothelial integrity related to atherosclerosis and to delineate the underlying mechanism. We found that XBP1 was highly expressed at branch points and areas of atherosclerotic lesions in the arteries of ApoE ؊/؊ mice, which was related to the severity of lesion development. In vitro study using human umbilical vein endothelial cells (HUVECs) indicated that disturbed flow increased the activation of XBP1 expression and splicing. Overexpression of spliced XBP1 induced apoptosis of HUVECs and endothelial loss from blood vessels during ex vivo cultures because of caspase activation and down-regulation of VE-cadherin resulting from transcriptional suppression and matrix metalloproteinase-mediated degradation. Reconstitution of VEcadherin by Ad-VEcad significantly increased Ad-XBP1s-infected HUVEC survival. Importantly, Ad-XBP1s gene transfer to the vessel wall of ApoE ؊/؊ mice resulted in development of atherosclerotic lesions after aorta isografting. These results indicate that XBP1 plays an important role in maintaining endothelial integrity and atherosclerosis development, which provides a potential therapeutic target to intervene in atherosclerosis.caspase ͉ endothelial integrity ͉ Ve-cadherin ͉ vessel graft ͉ mouse model A therosclerosis is a leading cause of death worldwide (1, 2).Accumulating evidence suggests that atherosclerosis is a multifactorial disease that can be initiated by risk factors (3-6). An important feature of atherosclerosis is its geographic distribution along the artery wall, i.e., occurring more frequently at curved or branching points in the vasculature, indicating that the flow pattern exerts an important role in the development of atherosclerotic lesions (7,8).Endothelial cells (ECs) are key cellular components of blood vessels, functioning as selectively permeable barriers between blood and tissues. It is believed that risk factors induce EC apoptosis, leading to the denudation or dysfunction of the intact endothelial monolayer, which causes lipid accumulation, monocyte adhesion, and inflammatory reactions that initiate atherosclerotic lesion (5, 9-12). Although information on risk factorinduced atherosclerosis has been accumulating, the underlying mechanism remains unclear.The X-box binding protein 1 (XBP1) was originally identified as a bZIP protein capable of binding to the cis-acting X box present in the promoter regions of human major histocompatibility complex class II genes (13) and is known to be essential for liver growth and B lymphocyte differentiation (14,15). In mammalian cells, XBP1 is a key signal transducer in the endoplasmic reticulum (ER) stress response. It has also been reported that there is a link between XBP1 and human disease (16,17). Although ER stress is reported to be involved in atherosclerosis (18)(19)(20)(21)(22), the role of XB...

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Arsenite induces endothelial cytotoxicity by down-regulation of vascular endothelial nitric oxide synthase

Cited by 59 publications

References 40 publications

Decreased Nitric Oxide Production in the Rat Brain after Chronic Arsenic Exposure

Decreased Nitric Oxide Production in the Rat Brain after Chronic Arsenic Exposure

Cardiovascular effects of arsenic: clinical and epidemiological findings

Sustained activation of XBP1 splicing leads to endothelial apoptosis and atherosclerosis development in response to disturbed flow

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