Oxysterols inhibit gap junctional communication between rat hepatocytes in primary culture.
Several oxysterols were examined for their effect on gap junctional communication between rat hepatocytes in primary culture. 25-Hydroxycholesterol, 22(S)-hydroxycholesterol and 7 beta-hydroxycholesterol, in decreasing order of potency, markedly inhibited gap junctional communication. In contrast, 7-ketocholesterol showed no inhibitory effect. The inhibition of gap junctional communication by oxysterols was not a consequence of changes in cell viability, as measured by lactate dehydrogenase leakage and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction activity. The addition of exogenous cholesterol to the culture medium did not abolish the effect of 25-hydroxycholesterol, suggesting that the capacity of oxysterols to inhibit gap junctional communication is independent of their inhibitory effect on cholesterol synthesis. We suppose that inhibition of gap junctional communication may be an early sign of oxysterols-induced toxicity on hepatocytes.
Guo
X
X
Division of Pharmacology, National Institute of Hygienic Sciences, Tokyo, Japan.
Ohno
Y
Y
Miyajima
A
A
Sunouchi
M
M
Takanaka
A
A
D000818:Animals; D002450:Cell Communication / Q000187:drug effects*; D002478:Cells, Cultured; D002784:Cholesterol / Q000494:pharmacology*; D006888:Hydroxycholesterols / Q000494:pharmacology*; D007365:Intercellular Junctions / Q000187:drug effects*; D007653:Ketocholesterols / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013778:Tetrazolium Salts; D013844:Thiazoles
D006888:Hydroxycholesterols; D007653:Ketocholesterols; D013778:Tetrazolium Salts; D013844:Thiazoles; D002784:Cholesterol; D007770:L-Lactate Dehydrogenase; C022616:thiazolyl blue