title: WNK-OSR1/SPAK-NCC signal cascade has circadian rhythm dependent on aldosterone.
abstract: Blood pressure and renal salt excretion show circadian rhythms. Recently, it has been clarified that clock genes regulate circadian rhythms of renal transporter expression in the kidney. Since we discovered the WNK-OSR1/SPAK-NaCl cotransporter (NCC) signal cascade, which is important for regulating salt balance and blood pressure, we have sought to determine whether NCC protein expression or phosphorylation shows diurnal rhythms in the mouse kidneys. Male C57BL/6J mice were sacrificed every 4h (at 20:00, 0:00, 4:00, 8:00, 12:00, and 16:00), and the expression and phosphorylation of WNK4, OSR1, SPAK, and NCC were determined by immunoblot. (Lights were turned on at 8:00, which was the start of the rest period, and turned off at 20:00, which was the start of the active period, since mice are nocturnal.) Although expression levels of each protein did not show diurnal rhythm, the phosphorylation levels of OSR1, SPAK, and NCC were increased around the start of the active period and decreased around the start of the rest period. Oral administration of eplerenone (10mg/day) attenuated the phosphorylation levels of these proteins and also diminished the diurnal rhythm of NCC phosphorylation. Thus, the activity of the WNK4-OSR1/SPAK-NCC cascade was shown to have a diurnal rhythm in the kidney that may be governed by aldosterone.
authors.affiliation: Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo, Tokyo 113-8519, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Susa
authors.forename: Eisei
authors.initials: E
authors.lastname: Sohara
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Isobe
authors.forename: Motoko
authors.initials: M
authors.lastname: Chiga
authors.forename: Tatemitsu
authors.initials: T
authors.lastname: Rai
authors.forename: Sei
authors.initials: S
authors.lastname: Sasaki
authors.forename: Shinichi
authors.initials: S
authors.lastname: Uchida
mesh_terms: D000450:Aldosterone / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism*; D015398:Signal Transduction; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters / Q000378:metabolism*
chemical_list: D011955:Receptors, Drug; C578875:Slc12a3 protein, mouse; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; D000450:Aldosterone; C499024:Prkwnk4 protein, mouse; C486407:Stk39 protein, mouse; C534421:OXSR1 protein, mouse; D017346:Protein Serine-Threonine Kinases