Unliganded RXR acts as an inhibitory factor on troglitazone-induced activation.
Troglitazone (TZ), a thiazolidinedione derivative, is a specific ligand for the peroxisome proliferator-activated receptor (PPAR) gamma and improves insulin sensitivity. PPARgamma regulates the expression of genes by binding to PPAR response element in promoter regions of regulator genes as heterodimers with a retinoid X receptor (RXR). We report here that PPARgamma activation by TZ depends on the expression levels of RXR. A transient transfection study in CV-1 cells revealed that the activation by TZ was suppressed by increasing amounts of expression of RXR, but not PPARgamma. Northern blot analysis revealed that PPARgamma and RXR were not expressed in CV-1 cells, and TZ did not induce PPARgamma or RXR mRNA in CV-1 cells indicating that RXR suppression is not related to these endogenous receptor expressions. Electrophoretic mobility shift assay revealed that the increasing amount of RXR did not compete with the DNA binding of the PPARgamma/RXR heterodimer in the presence or absence of TZ. Transfected co-activators enhanced the TZ-dependent gene transcription, and this activation was inhibited by excessive amounts of RXR, indicating that unliganded RXR may recruit the specific coactivators from the PPARgamma/RXR heterodimer.
Monden
Tsuyoshi
T
Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Shimotsuga-gun, Tochigi 321-0293, Japan. mondent@dokkyomed.ac.jp
Yamada
Masanobu
M
Nihei
Yasuyo
Y
Kishi
Mikiko
M
Tomaru
Takuya
T
Ishii
Sumiyasu
S
Hashida
Tetsu
T
Shibusawa
Nobuyuki
N
Hashimoto
Koshi
K
Satoh
Teturou
T
Kasai
Kikuo
K
Mori
Masatomo
M
D000818:Animals; D015152:Blotting, Northern; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D002839:Chromans / Q000494:pharmacology*; D051548:Histone Acetyltransferases; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007668:Kidney / Q000166:cytology; D008024:Ligands; D051379:Mice; D056920:Nuclear Receptor Coactivator 1; D047495:PPAR gamma / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D047488:Retinoid X Receptors / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D045162:Thiazolidinediones / Q000494:pharmacology*; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D000077288:Troglitazone
D002839:Chromans; D007004:Hypoglycemic Agents; D008024:Ligands; D047495:PPAR gamma; D012333:RNA, Messenger; D047488:Retinoid X Receptors; D045162:Thiazolidinediones; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; C538861:Ncoa1 protein, mouse; D056920:Nuclear Receptor Coactivator 1; D000077288:Troglitazone