Calcium and Calmodulin Regulate Mercury-induced Phospholipase D Activation in Vascular Endothelial Cells

Peltz, Alon; Sherwani, Shariq I.; Kotha, Sainath R.; Mazerik, Jessica N.; Butler, Elizabeth Susan O’Connor; Kuppusamy, M. Lakshmi; Hagele, Thomas; Magalang, Ulysses J.; Kuppusamy, Periannan; Marsh, Clay B.; Parinandi, Narasimham L.

doi:10.1177/1091581809338077

Cited by 17 publications

(14 citation statements)

References 55 publications

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“…Similarly, Seppänen et al (2004) found no evidence for promotion of direct lipid peroxidation by MeHg. Other in vitro studies have provided support for the hypothesis that MeHg can interfere with signal transduction and proper endothelial cell function [both in human umbilical cord endothelial cells (Hagele et al 2007; Mazerik et al 2007; Peltz et al 2009) and bovine endothelial cells (Kishimoto et al 1995; Ohno et al 1995)], which may influence atherosclerosis. However, three studies support a direct mechanism for MeHg’s role in oxidation, showing that antioxidants and compounds that remove ROS can mitigate MeHg toxicity (Gasso et al 2001; Park et al 1996; Welsh 1979).…”

Section: Workhop Findings and Near-term Recommendationsmentioning

confidence: 94%

Evaluation of the Cardiovascular Effects of Methylmercury Exposures: Current Evidence Supports Development of a Dose–Response Function for Regulatory Benefits Analysis

Roman¹,

Walsh²,

Coull

et al. 2011

Environ Health Perspect

211

130

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BackgroundThe U.S. Environmental Protection Agency (U.S. EPA) has estimated the neurological benefits of reductions in prenatal methylmercury (MeHg) exposure in past assessments of rules controlling mercury (Hg) emissions. A growing body of evidence suggests that MeHg exposure can also lead to increased risks of adverse cardiovascular impacts in exposed populations.Data extractionThe U.S. EPA assembled the authors of this article to participate in a workshop, where we reviewed the current science concerning cardiovascular health effects of MeHg exposure via fish and seafood consumption and provided recommendations concerning whether cardiovascular health effects should be included in future Hg regulatory impact analyses.Data synthesisWe found the body of evidence exploring the link between MeHg and acute myocardial infarction (MI) to be sufficiently strong to support its inclusion in future benefits analyses, based both on direct epidemiological evidence of an MeHg–MI link and on MeHg’s association with intermediary impacts that contribute to MI risk. Although additional research in this area would be beneficial to further clarify key characteristics of this relationship and the biological mechanisms that underlie it, we consider the current epidemiological literature sufficiently robust to support the development of a dose–response function.ConclusionsWe recommend the development of a dose–response function relating MeHg exposures with MIs for use in regulatory benefits analyses of future rules targeting Hg air emissions.

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Section: Workhop Findings and Near-term Recommendationsmentioning

confidence: 94%

Evaluation of the Cardiovascular Effects of Methylmercury Exposures: Current Evidence Supports Development of a Dose–Response Function for Regulatory Benefits Analysis

Roman¹,

Walsh²,

Coull

et al. 2011

Environ Health Perspect

211

130

View full text Add to dashboard Cite

show abstract

“…In regard to general brain health, both forms of Hg (Me- and Et-Hg) have been found to cause Hg-induced vasculo-toxicity and resulting reduced blood flow in the brain [117,118,119]. Both cerebral and cerebellar decreased blood flow can result from Hg exposure.…”

Section: Research Evidencementioning

confidence: 99%

Thimerosal Exposure and the Role of Sulfation Chemistry and Thiol Availability in Autism

Kern

Haley

Geier

et al. 2013

IJERPH

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Autism spectrum disorder (ASD) is a neurological disorder in which a significant number of the children experience a developmental regression characterized by a loss of previously acquired skills and abilities. Typically reported are losses of verbal, nonverbal, and social abilities. Several recent studies suggest that children diagnosed with an ASD have abnormal sulfation chemistry, limited thiol availability, and decreased glutathione (GSH) reserve capacity, resulting in a compromised oxidation/reduction (redox) and detoxification capacity. Research indicates that the availability of thiols, particularly GSH, can influence the effects of thimerosal (TM) and other mercury (Hg) compounds. TM is an organomercurial compound (49.55% Hg by weight) that has been, and continues to be, used as a preservative in many childhood vaccines, particularly in developing countries. Thiol-modulating mechanisms affecting the cytotoxicity of TM have been identified. Importantly, the emergence of ASD symptoms post-6 months of age temporally follows the administration of many childhood vaccines. The purpose of the present critical review is provide mechanistic insight regarding how limited thiol availability, abnormal sulfation chemistry, and decreased GSH reserve capacity in children with an ASD could make them more susceptible to the toxic effects of TM routinely administered as part of mandated childhood immunization schedules.

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“…The amplitude and kinetics of both transient and sustained phases of hypoxia-induced pulmonary vasoconstriction are not significantly changed in isolated perfused lungs from BKα –/– mice or hemogenase-2 knock-out mice (HO-2 –/– ). These data indicate that, although BK Ca channels are regulated by HO-2-mediated redox changes, the HO-2/BK Ca complex may not serve as an oxygen sensor in acute hypoxia-induced pulmonary vasoconstriction (218, 245). …”

Section: K+ Channels and Transportersmentioning

confidence: 90%

Endothelial and Smooth Muscle Cell Ion Channels in Pulmonary Vasoconstriction and Vascular Remodeling

Makino

Firth

Yuan

2011

Comprehensive Physiology

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The pulmonary circulation is a low resistance and low pressure system. Sustained pulmonary vasoconstriction and excessive vascular remodeling often occur under pathophysiological conditions such as in patients with pulmonary hypertension. Pulmonary vasoconstriction is a consequence of smooth muscle contraction. Many factors released from the endothelium contribute to regulating pulmonary vascular tone, while the extracellular matrix in the adventitia is the major determinant of vascular wall compliance. Pulmonary vascular remodeling is characterized by adventitial and medial hypertrophy due to fibroblast and smooth muscle cell proliferation, neointimal proliferation, intimal, and plexiform lesions that obliterate the lumen, muscularization of precapillary arterioles, and in situ thrombosis. A rise in cytosolic free Ca2+ concentration ([Ca2+]cyt) in pulmonary artery smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction, while increased release of mitogenic factors, upregulation (or downregulation) of ion channels and transporters, and abnormalities in intracellular signaling cascades are key to the remodeling of the pulmonary vasculature. Changes in the expression, function, and regulation of ion channels in PASMC and pulmonary arterial endothelial cells play an important role in the regulation of vascular tone and development of vascular remodeling. This article will focus on describing the ion channels and transporters that are involved in the regulation of pulmonary vascular function and structure and illustrating the potential pathogenic role of ion channels and transporters in the development of pulmonary vascular disease.

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Calcium and Calmodulin Regulate Mercury-induced Phospholipase D Activation in Vascular Endothelial Cells

Cited by 17 publications

References 55 publications

Evaluation of the Cardiovascular Effects of Methylmercury Exposures: Current Evidence Supports Development of a Dose–Response Function for Regulatory Benefits Analysis

Evaluation of the Cardiovascular Effects of Methylmercury Exposures: Current Evidence Supports Development of a Dose–Response Function for Regulatory Benefits Analysis

Thimerosal Exposure and the Role of Sulfation Chemistry and Thiol Availability in Autism

Endothelial and Smooth Muscle Cell Ion Channels in Pulmonary Vasoconstriction and Vascular Remodeling

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