Effect of cadmium on gap junctional intercellular communication in primary cultures of rat renal proximal tubular cells.
Cadmium mainly accumulates in the kidney and causes renal injury. To clarify the mechanism of Cd nephrotoxicity, we investigated the effects of this element on intercellular communication through gap junction channels in primary cultures of rat renal proximal tubular cells. Sixty minutes after exposure to 100 microM Cd, dye coupling experiments showed that gap junctional intercellular communication (GJIC) was significantly inhibited. This inhibition occurred before the appearance of cytotoxicity. Intracellular calcium concentrations [Ca2+]i, which modulate the function of gap junctions, gradually increased after exposure to Cd and reached a maximum after 60 minutes. These results suggest that the inhibition of GJIC as a result of Cd exposure is related to an increase in [Ca2+]i, and that GJIC inhibition may be an indicator of nephrotoxicity.
Fukumoto
M
M
Department of Internal Medicine II, The Jikei University School of Medicine, Tokyo, Japan.
Kujiraoka
T
T
Hara
M
M
Shibasaki
T
T
Hosoya
T
T
Yoshida
M
M
D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D019256:Cadmium Chloride / Q000633:toxicity*; D002450:Cell Communication / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D017629:Gap Junctions / Q000187:drug effects* / Q000648:ultrastructure; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009566:Nitrates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D009566:Nitrates; D007770:L-Lactate Dehydrogenase; D000118:Acetylglucosaminidase; D019256:Cadmium Chloride