Találati lista | Tudóstér

001-es BibID:	BIBFORM060362
Első szerző:	Geyer Nikolett
Cím:	Bile acids activate ryanodine receptors in pancreatic acinar cells via a direct allosteric mechanism / Geyer Nikolett, Diszházi Gyula, Csernoch László, Jóna István, Almássy János
Dátum:	2015
ISSN:	0143-4160
Megjegyzések:	The earliest critical event of pancreatitis is a long lasting high amplitude rise of intracellular Ca(2+) concentration of the acinar cell, which can be triggered by high concentration of bile acids. Although, Ca(2+)-release through ryanodine receptors (RyR) is involved in the process, the significance and the exact mechanism of bile acid's action on RyR has not been fully elucidated yet. Therefore, we aimed to test with various techniques and aspects whether bile acids exert a direct effect on RyR and SERCA pump. Our data show that taurocholic acid (TCA)-induced Ca(2+) release in pancreatic acinar cells was significantly reduced by the RyR antagonist dantrolene. Further, we show that TCA enhanced RyR's (3)H-ryanodine binding and triggered robust Ca(2+)-release from RyR-enriched vesicles in the pathologically relevant concentration range. RyR single channel current analysis demonstrated that 200?M TCA induced a 5-fold increase in the channel's open probability and caused a significant lengthening of the mean open time. TCA also suppressed Ca(2+)-uptake rate and ATP-ase activity of SERCA-enriched vesicles, but interestingly, failed to decrease Ca(2+) elimination rate in intact cells. Overall, our results strongly suggest that TCA opens RyR by an allosteric mechanism, which contribute significantly to bile acid-induced pathologic Ca(2+)-leak from the endoplasmic reticulum in pancreatic acinar cells.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban ryanodine receptor SERCA Calcium release Pancreas Bile acid
Megjelenés:	Cell Calcium. - 58 : 2 (2015), p. 160-170. -
További szerzők:	Diszházi Gyula (1992-) (gyógyszerész) Csernoch László (1961-) (élettanász) Jóna István (1948-) (élettanász, fizikus) Almássy János (1981-) (élettanász, biológus, angol-magyar szakfordító)
Pályázati támogatás:	112199 OTKA
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon: