Találati lista | Tudóstér

001-es BibID:	BIBFORM082980
035-os BibID:	(WoS)000511350000001 (Scopus)85079060274 (PubMed)31917868
Első szerző:	Fanczal Júlia
Cím:	TRPM2-mediated extracellular Ca2+ entry promotes acinar cell necrosis in biliary acute pancreatitis / Júlia Fanczal, Petra Pallagi, Marietta Görög, Gyula Diszházi, János Almássy, Tamara Madácsy, Árpád Varga, Péter Csernay-Biró, Xénia Katona, Emese Tóth, Réka Molnár, Zoltán Rakonczay, Péter Hegyi, József Maléth
Dátum:	2020
ISSN:	0022-3751 1469-7793
Megjegyzések:	Acute biliary pancreatitis poses a significant clinical challenge as currently no specific pharmaceutical treatment exists. Disturbed intracellular Ca2+ signalling caused by bile acids is a hallmark of the disease, which induces increased reactive oxygen species (ROS) production, mitochondrial damage, intra-acinar digestive enzyme activation and cell death. Because of this mechanism of action, prevention of toxic cellular Ca2+ overload is a promising therapeutic target. Transient Receptor Potential Melastatin 2 (TRPM2) is a non-selective cation channel that has recently emerged as an important contributor to oxidative-stress-induced cellular Ca2+ overload across different diseases. However, the expression and possible functions of TRPM2 in the exocrine pancreas remain unknown. Here we found that TRPM2 is expressed in the plasma membrane of mouse pancreatic acinar and ductal cells, which can be activated by increased oxidative stress induced by H2O2 treatment. TRPM2 activity was found to contribute to bile acid-induced extracellular Ca2+ influx in acinar cells, but did not have the same effect in ductal cells. The generation of intracellular ROS in response to bile acids was remarkably higher in pancreatic acinar cells compared to isolated ducts, which can explain the difference between acinar and ductal cells. This activity promoted acinar cell necrosis in vitroindependently from mitochondrial damage or mitochondrial fragmentation. In addition, bile-acid-induced experimental pancreatitis was less severe in TRPM2 knockout mice, whereas the lack of TRPM2 had no protective effect in cerulein induced acute pancreatitis. Our results suggest that the inhibition of TRPM2 may be a potential treatment option for biliary pancreatitis.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Ca2+ signalling TRPM2 channel acinar cell necrosis acute pancreatitis bile acid epithelial ion transport
Megjelenés:	Journal of Physiology. - 598 : 6 (2020), p. 1253-1270. -
További szerzők:	Pallagi Petra Görög Marietta Diszházi Gyula (1992-) (gyógyszerész) Almássy János (1981-) (élettanász, biológus, angol-magyar szakfordító) Madácsy Tamara Varga Árpád Csernay-Biró Péter Katona Xénia Tóth Emese Molnár Réka Rakonczay Zoltán Hegyi Péter Jenő (belgyógyász) Maléth József
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon:

001-es BibID:	BIBFORM127812
035-os BibID:	(Scopus)85208330047 (WoS)001381334300001
Első szerző:	Geyer Nikolett
Cím:	Ca2+ signaling of pancreatic acinar cells in malignant hyperthermia susceptibility / Nikolett Geyer, Gyula Diszházi, Zsuzsanna É. Magyar, Beatrix Dienes, Réka Csáki, Péter Enyedi, Tamara Madácsy, József Maléth, János Almássy
Dátum:	2024
ISSN:	1424-3903
Megjegyzések:	Background: Malignant hyperthermia susceptibility (MHS) and acute pancreatitis (AP) share a common cellular pathomechanism that is Ca2+-overload of the muscle fiber and the pancreatic acinar cell (PAC). In the muscle, gain-of-function mutations of the ryanodine receptor (RyR1) make the Ca2+-release mechanism hypersensitive to certain ligands, including Ca2+, volatile anaesthetics and succinylcholine, creating a medical emergency when the patient is exposed to these drugs. As RyR1 was shown to contribute to Ca2+-overload in PAC, we presumed that pancreata of MHS individuals are more prone to AP. Accordingly, a recent case study reported coincidence of MHS with recurrent AP, indicating a pathological link between the two diseases. Methods: We tested if MHS poses a risk for AP in mice carrying the Y522S MHS mutation. Fluorescent Ca2+ imaging was performed in PACs. Conventional histopathological analysis and plazma amylase measurement was performed using a cerulein-induced pancreatitis mouse model. Results: The intracellular Ca2+-signals of PACs from MHS mice were slightly bigger then in wild type when stimulated with 0.2 and 2 ?M carbachol (cch) or with 1 and 5 mM bile acid (taurocholic acid). Store-operated-Ca2+-entry was also higher in PACs from MHS mice. Nevertheless, histopathological analysis and plasma amylase levels did not indicate more severe AP in MHS. Conclusions: These results suggest that the Y522S RyR1 mutation alter the Ca2+-homeostasis in PACs, but not as much as to cause or aggravate AP.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Acute pancreatitis Calcium signaling Malignant hyperthermia Pancreatic acinar cells Ryanodine receptor
Megjelenés:	Pancreatology. - 24 : 8 (2024), p. 1257-1264. -
További szerzők:	Diszházi Gyula (1992-) (gyógyszerész) Magyar Zsuzsanna Édua (1993-) (molekuláris biológus) Dienes Beatrix (1972-) (élettanász, molekuláris biológus) Csáki Réka Enyedi Péter Madácsy Tamara Maléth József Almássy János (1981-) (élettanász, biológus, angol-magyar szakfordító)
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon: