title: Methylmercury inhibits gap junctional intercellular communication in primary cultures of rat proximal tubular cells.
abstract: Methylmercury (MeHg) causes renal injury in addition to central and peripheral neuropathy. To clarify the mechanism of nephrotoxicity by MeHg, we investigated the effect of this compound on intercellular communication through gap junction channels in primary cultures of rat renal proximal tubular cells. Twenty minutes after exposure to 30 microM MeHg, gap junctional intercellular communication (GJIC), which was assessed by dye coupling, was markedly inhibited before appearance of cytotoxicity. When the medium containing MeHg was exchanged with MeHg-free medium, dye coupling recovered abruptly. However, the dye-coupling was abolished again 30 min after replacement with control medium, and the cells were damaged. Intracellular calcium concentration, [Ca2+]i, which modulates the function of gap junctions, significantly increased following exposure of the cells to 30 microM MeHg and returned to control level following replacement with MeHg-free medium. These results suggest that the inhibiting effect of MeHg on GJIC is related to the change in [Ca2+]i, and may be involved in the pathogenesis of renal dysfunction.
authors.affiliation: Department of Chemistry, St. Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yoshida
authors.forename: T
authors.initials: T
authors.lastname: Kujiraoka
authors.forename: M
authors.initials: M
authors.lastname: Hara
authors.forename: H
authors.initials: H
authors.lastname: Nakazawa
authors.forename: Y
authors.initials: Y
authors.lastname: Sumi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002450:Cell Communication; D002478:Cells, Cultured; D017629:Gap Junctions / Q000187:drug effects*; D007687:Kidney Tubules, Proximal / Q000187:drug effects*; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008767:Methylmercury Compounds; D009569:Nitric Oxide; D002118:Calcium