期刊
TOXICOLOGY
卷 392, 期 -, 页码 40-46出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2017.09.013
关键词
Methylmercury; Minamata disease; Cerebral edema; Prostaglandin
资金
- Fund of the Overall Study on the Health Effects of Heavy Metals (Overall Study on Minamata disease) Project of Ministry of the Environment (MOE), Japan
- JSPS KAKENHI Grant [JP15K21405]
Methylmercury is an environmental pollutant that exhibits neurotoxicity when ingested, primarily in the form of neuropathological lesions that localize along deep sulci and fissures, in addition to edematous and inflammatory changes in patient cerebrums. These conditions been known to give rise to a variety of ailments that have come to be collectively termed Minamata disease. Since prostaglandins I-2 and E-2 (PGI(2) and PGE(2)) increase vascular permeability and contribute to the progression of inflammatory changes, we hypothesize that methylmercury induces the synthesis of these prostaglandins in brain microvascular endothelial cells and pericytes. To test this theory, human brain microvascular endothelial cells and pericytes were cultured and treated with methylmercury, after which the PGI(2) and PGE(2) released from endothelial cells and/or pericytes were quantified by enzyme linked immunosorbent assay while protein and mRNA expressions in endothelial cells were analyzed by western blot analysis and real-time reverse transcription polymerase chain reaction, respectively. Experimental results indicate that methylmercury inhibits the activity of protein tyrosine phosphatase 1B, which in turn activates the epidermal growth factor receptor p38 mitogen-activated protein kinase pathway that induces cyclooxygenase-2 expression. It was also found that the cyclic adenosine 3',5'-monophosphate pathway, which can be activated by PGI(2) and PGE(2), is involved in methylmercury-induced cyclooxygenase-2 expression. Since it appears that protein tyrosine phosphatase 1 B serves as a sensor protein for methylmercury in these mechanisms, it is our belief that the results of the present study may provide additional insights into the molecular mechanisms responsible for edematous and inflammatory changes in the cerebrum of patients with Minamata disease.
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