The Cytotoxicity of Methylmercury in Human Microvascular Endothelial Cells and Pericytes in Culture

Abstract

Methylmercury is an environmental neurotoxin that induces severe neurological damage in the brain of humans and animals. The main pathological characteristic of methylmercury neurotoxicity is the location of the damage; lesions are localized around the deep sulci and fissures in the cerebral cortex, such as the calcarine fissure, and the granule cell layer of the cerebellum. Since the localization of the damage is suggested to be a result of secondary damage occurring due to edematous change in the white cortex, the toxicity of methylmercury to cells that compose the microvessels-endothelial cells and pericytes-may be important for understanding the neurotoxicity of methylmercury. We investigated the toxicity of methylmercury to human brain microvascular endothelial cells and pericytes using a cell culture system. It was revealed that the toxicity of methylmercury to microvascular cells depends on the cell type and density. It is suggested that vascular tissue is one of the targets of methylmercury toxicity and that this may contribute to the progression of edematous change in the brain. Methylmercury may also be involved in the progression of cardiovascular diseases.

Pericytes: brain-immune interface modulators

“…The inflammatory response to a foreign agent may cause irreversible brain damage by continuous exposure to pathogen-derived toxic molecules and immune mediators (Kumar et al, 2009; Hirooka and Kaji, 2012). Factors that promote a pro-inflammatory state in the brain include abiotic agents such as heavy metal ions or viruses, and biotic factors such as bacteria, fungi, and parasites (Gasque et al, 1998; Liou and Hsu, 1998; Alvarez and Teale, 2007; Hirooka and Kaji, 2012; Nakagawa et al, 2012).…”

“…Factors that promote a pro-inflammatory state in the brain include abiotic agents such as heavy metal ions or viruses, and biotic factors such as bacteria, fungi, and parasites (Gasque et al, 1998; Liou and Hsu, 1998; Alvarez and Teale, 2007; Hirooka and Kaji, 2012; Nakagawa et al, 2012). There is scant knowledge of pericyte function and structure under inflammatory response induced by foreign agents.…”

“…The methionine-like complex enters the brain by the large neutral amino acid transporter (LAT-1); once inside, the heavy metal ions induce cytokine and growth factor release by blood–brain barrier components. Heavy metal ions associate with the fibroblast growth factor type 2 (FGF-2); this union may cause cell damage because FGF-2 is unable to repair endothelial damage; therefore, heavy metal ions promote less auto-regulatory signaling inhibition of EC proliferation (Hirooka and Kaji, 2012). …”

Participación de mediadores inflamatorios en la alteración estructural y funcional de la barrera hematoencefálica inducida por la restricción de sueño

“…The inflammatory response to a foreign agent may cause irreversible brain damage by continuous exposure to pathogenderived toxic molecules and immune mediators (Kumar et al, 2009;Hirooka and Kaji, 2012). Factors that promote a proinflammatory state in the brain include abiotic agents such as heavy metal ions or viruses, and biotic factors such as bacteria, fungi, and parasites (Gasque et al, 1998;Liou and Hsu, 1998;Alvarez and Teale, 2007;Hirooka and Kaji, 2012;Nakagawa et al, 2012). There is scant knowledge of pericyte function and structure under inflammatory response induced by foreign agents.…”

“…The methionine-like complex enters the brain by the large neutral amino acid transporter (LAT-1); once inside, the heavy metal ions induce cytokine and growth factor release by blood-brain barrier components. Heavy metal ions associate with the fibroblast growth factor type 2 (FGF-2); this union may cause cell damage because FGF-2 is unable to repair endothelial damage; therefore, heavy metal ions promote less autoregulatory signaling inhibition of EC proliferation (Hirooka and Kaji, 2012).…”