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001-es BibID:BIBFORM035499
035-os BibID:(Scopus)79955543079 (WoS)000290559600012 (PMID)20726815
Első szerző:Petrovski, Goran (orvos)
Cím:Cardioprotection by endoplasmic reticulum stress-induced autophagy / Goran Petrovski, Somak Das, Bela Juhasz, Attila Kertesz, Arpad Tosaki, Dipak K. Das
Megjegyzések:This study tested the hypothesis that the induction of autophagy by producing therapeutic amounts of endoplasmicreticulum (ER) stress in the heart before an ischemic insult would ameliorate=reduce subsequent lethalmyocardial ischemic=reperfusion (I=R) injury (similar to ischemic preconditioning). A dose?response study withboth tunicamycin and thapsigargin was performed to determine the optimal dose (0.3mg=kg) for inducingautophagy for cardioprotection. The Sprague?Dawley rats weighing between 250 and 300 g were randomlyassigned into five groups: normal control (injected with saline only), high (3mg=kg), and low (0.3mg=kg) dosesof tunicamycin or thapsigargin, respectively. After 48 h, the rats were subjected to an isolated working heartpreparation: 30 min ischemia followed by 2 h of reperfusion with continuous left ventricular function monitoring.At the end, the hearts were subjected to either measurement of infarct size or cardiomyocyte apoptosis.Some hearts (from different sets of experiments) were used for transmission electron microscopy (TEM), confocalmicroscopy, or Western blot analysis. Tunicamycin and thapsigargin, irrespective of the dose, induced sufficientER stress, as evidenced by the increased phosphorylation or activation of eIF2a and PERK. Such ER stresspotentiated autophagy in the heart, as evidenced by an increase in LC3-II, beclin-1, and Atg5. This was alsosupported by TEM, clearly showing the production of autophagosomes, and by confocal microscopy, showingupregulation of eIF2a and beclin-1. The autophagy produced with lower doses of tunicamycin and thapsigarginin the face of myocardial I=R resulted in reduction of the I=R injury, as evidenced by improved left ventricularfunction and reduced myocardial infarct size and cardiomyocyte apoptosis. In concert, an induction of GRP78and activation of Akt and Bcl-2 occurred. The higher doses conversely were detrimental for the heart and wereassociated with induction of CHOP and downregulation of Akt. The results thus display the proof of conceptthat induction of autophagy by ER stress (therapeutic amount) before ischemia (similar to ischemic preconditioning)could reduce subsequent lethal ischemic reperfusion injury.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Antioxidants & redox signaling. - 14 : 11 (2011), p. 2191-2200. -
További szerzők:Das, Somak Juhász Béla (1978-) (kísérletes farmakológus) Kertész Attila Béla (1973-) (kardiológus) Tósaki Árpád (1958-) (kísérletes farmakológus, gyógyszerész) Das, Dipak Kumar
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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