Circadian coordination of ATP release in the urothelium via connexin43 hemichannels
| Autor: | Takeshi Sano, Masao Doi, Akihiro Kanematsu, Sumihiro Kunisue, Jin Kono, Atsushi Sengiku, Nobuyuki Nishikawa, Hitoshi Okamura, Shigeki Shimba, Osamu Ogawa, Louis S. Liou, Masakatsu Ueda, Hiromitsu Negoro, Kojiro Tsujihana |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell type Circadian clock lcsh:Medicine Connexin urologic and male genital diseases Article Cell Line 03 medical and health sciences chemistry.chemical_compound Mice Adenosine Triphosphate Animals Humans Circadian rhythm Mechanotransduction Urothelium lcsh:Science Aged Multidisciplinary lcsh:R ARNTL Transcription Factors female genital diseases and pregnancy complications Cell biology Circadian Rhythm CLOCK Mice Inbred C57BL 030104 developmental biology chemistry Connexin 43 cardiovascular system lcsh:Q Female sense organs biological phenomena cell phenomena and immunity Adenosine triphosphate |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-11 (2018) |
| ISSN: | 2045-2322 |
| Popis: | Day-night changes in the storage capacity of the urinary bladder are indispensable for sound sleep. Connexin 43 (Cx43), a major gap junction protein, forms hemichannels as a pathway of ATP in other cell types, and the urinary bladder utilizes ATP as a mechanotransduction signals to modulate its capacity. Here, we demonstrate that the circadian clock of the urothelium regulates diurnal ATP release through Cx43 hemichannels. Cx43 was expressed in human and mouse urothelium, and clock genes oscillated in the mouse urothelium accompanied by daily cycles in the expression of Cx43 and extracellular ATP release into the bladder lumen. Equivalent chronological changes in Cx43 and ATP were observed in immortalized human urothelial cells, but these diurnal changes were lost in both arrhythmic Bmal1-knockout mice and in BMAL1-knockdown urothelial cells. ATP release was increased by Cx43 overexpression and was decreased in Cx43 knockdown or in the presence of a selective Cx43 hemichannel blocker, which indicated that Cx43 hemichannels are considered part of the components regulating ATP release in the urothelium. Thus, a functional circadian rhythm exists in the urothelium, and coordinates Cx43 expression and function as hemichannels that provide a direct pathway of ATP release for mechanotransduction and signalling in the urothelium. |
| Databáze: | OpenAIRE |
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