Retinol-induced mdr1 and mdr3 modulation in cultured rat Sertoli cells is attenuated by free radical scavengers.
The effects of retinol on modulation of mdr genes in Sertoli cells were investigated. The hypothesis that free radical scavengers may attenuate the effect of retinol was also tested. Sertoli cells isolated from 15-day-old Wistar rats were cultured for 48 h and then treated with retinol for 24 h with or without free radical scavengers (1 mM mannitol, 0.1 mM Trolox or superoxide dismutase [200 U/ml]). Expression of mdr1, mdr2 and mdr3 genes was monitored by RT-PCR. Mitochondrial superoxide production was used as an index of ROS production. Expression of mdr1 and mdr3 was inhibited by retinol treatment (7 microM, 24 h), while mdr2 was not detected in response to any of the treatments. We also observed that retinol supplementation (7 microM, 24 h) increased superoxide production. The observed inhibition of mdr genes was attenuated by all co-treatments, suggesting that retinol-induced ROS are required for inhibition of mdr1 and mdr3 expression. The results suggest that retinol may play an important role in the modulation of the mdr gene family in cultured rat Sertoli cells and that these effects appear to be mediated by ROS.
Centro de Estudos em Estresse Oxidativo (CEEO), ICBS -- UFRGS, Porto Alegre, Brazil. mfrotajr@yahoo.com.br
Mário Luiz Conte da
ML
Frota
Fábio
F
Klamt
Felipe
F
Dal-Pizzol
Marion
M
Schiengold
José Cláudio Fonseca
JC
Moreira
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism*; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D016166:Free Radical Scavengers / Q000378:metabolism*; D006801:Humans; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012708:Sertoli Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D014801:Vitamin A / Q000494:pharmacology*
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D014801:Vitamin A; C095122:multidrug resistance protein 3