title: Effects of TCDD and estradiol-17beta on the proliferation and Na+/glucose cotransporter in renal proximal tubule cells.
abstract: TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is a highly toxic environmental toxicant that alters cell proliferation and function. Estrogens are noted for their ability to stimulate cell proliferation in various tissues. However, little is known about any interaction between TCDD and estradiol-17beta (E(2)) that affects renal proximal tubule cell proliferation and Na(+)/glucose cotransporters' activity. Thus, the effects of TCDD and E(2) on [(3)H]-thymidine incorporation and on alpha-methyl-d-glucopyranoside (alpha-MG) uptake were investigated in the primary rabbit kidney proximal tubule cells (PTCs). TCDD (>10(-10) M >1 h) inhibited [(3)H]-thymidine incorporation and c-fos transcripts in real-time RT-PCR, whereas E(2) (>10(-9) M, 24 h) stimulated them. Aryl hydrocarbon receptor (AhR) agonists, beta-naphthoflavone (beta-NF) and polychlorinated biphenyls (PCBs) (10(-6) M) synergistically increased the TCDD-induced inhibition of [(3)H]-thymidine incorporation. However, the AhR antagonist, alpha-naphthoflavone (alpha-NF) as well as E(2) blocked TCDD-induced inhibition of [(3)H]-thymidine incorporation. TCDD (10(-8) M, 48 h) specifically inhibited alpha-MG uptake and its effect was due to V(max) value but not K(m) value. Indeed, TCDD decreased Na(+)/glucose cotransporter 1, 2 (SGLT1, 2) protein level compared with control. In addition, TCDD-induced inhibition of alpha-MG uptake was blocked by alpha-NF or E(2). In conclusion, TCDD inhibited [(3)H]-thymidine incorporation and alpha-MG uptake, and E(2) blocked TCDDs effects in primary cultured renal proximal tubule cells.
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Biotechnology Research Institute, Chonnam National University, Gwangju 500-757, South Korea. hjhan@chonnam.ac.kr
authors.forename: Ho Jae
authors.initials: HJ
authors.lastname: Han
authors.forename: Min Jin
authors.initials: MJ
authors.lastname: Lim
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Lee
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Kim
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Jang Hern
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004785:Environmental Pollutants / Q000633:toxicity*; D004958:Estradiol / Q000633:toxicity*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008757:Methylglucosides / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D011078:Polychlorinated Biphenyls / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051269:Sodium-Glucose Transporter 1; D019324:beta-Naphthoflavone / Q000494:pharmacology
chemical_list: D001571:Benzoflavones; D004785:Environmental Pollutants; D008562:Membrane Glycoproteins; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D000072317:Polychlorinated Dibenzodioxins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D051269:Sodium-Glucose Transporter 1; D004958:Estradiol; C027020:methylglucoside; C011512:alpha-naphthoflavone; D019324:beta-Naphthoflavone; D011078:Polychlorinated Biphenyls