Hydration status affects nuclear distribution of transcription factor tonicity responsive enhancer binding protein in rat kidney.
Tonicity responsive enhancer binding protein (TonEBP) is the transcription factor that regulates tonicity responsive expression of proteins that catalyze cellular accumulation of compatible osmolytes. In cultured MDCK cells, hypertonicity stimulates the activity of TonEBP via a combination of increased protein abundance and increased nuclear localization. For investigating regulation of TonEBP in the kidney, rats were subjected to water loading or dehydration. Water loading lowered urine osmolality and mRNA expression of sodium/myo-inositol cotransporter (SMIT), a target gene of TonEBP, in the renal medulla; dehydration doubled the urine osmolality and increased SMIT mRNA expression. In contrast, overall abundance of TonEBP and its mRNA measured by immunoblot and ribonuclease protection assay, respectively, was not affected. Immunohistochemical analysis, however, revealed that nuclear distribution of TonEBP is generally increased throughout the medulla in dehydrated animals compared with water loaded animals. Increased nuclear localization was particularly dramatic in thin limbs. Notable exceptions were the middle to terminal portions of the inner medullary collecting ducts and blood vessels, where a change in TonEBP distribution was not evident. Immunohistochemical detection of SMIT mRNA revealed that the changes in nuclear distribution of TonEBP correlate with expression of SMIT. It is concluded that under physiologic conditions, nucleocytoplasmic distribution is the dominant mode of regulation of TonEBP in the renal medulla.
Cha
Jung H
JH
Department of Anatomy, Catholic University of Korea, Seoul, Korea.
Woo
Seung Kyoon
SK
Division of Nephrology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland.
Han
Ki H
KH
Department of Anatomy, Catholic University of Korea, Seoul, Korea.
Kim
Young H
YH
Department of Anatomy, Catholic University of Korea, Seoul, Korea.
Handler
Joseph S
JS
Division of Nephrology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland.
Kim
Jin
J
Department of Anatomy, Catholic University of Korea, Seoul, Korea.
Kwon
H Moo
HM
Division of Nephrology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland.
D000818:Animals; D001834:Body Water / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D003681:Dehydration / Q000378:metabolism; D004326:Drinking; D006360:Heat-Shock Proteins / Q000235:genetics; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters / Q000235:genetics; D014018:Tissue Distribution; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014556:Urine / Q000737:chemistry; D014868:Water Deprivation / Q000502:physiology
D006360:Heat-Shock Proteins; D008565:Membrane Proteins; C492199:Nfat5 protein, rat; D012333:RNA, Messenger; D027981:Symporters; D015534:Trans-Activators; D014157:Transcription Factors; C073884:SLC5A3 protein, human