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001-es BibID:	BIBFORM072791
Első szerző:	Barta Tünde
Cím:	Endothelin-1-induced hypertrophic alterations and heme oxygenase-1 expression in cardiomyoblasts are counteracted by beta estradiol : in vitro and in vivo studies / Tunde Barta, Agnes Tosaki, David Haines, Gyorgy Balla, Istvan Lekli, Arpad Tosaki
Dátum:	2018
ISSN:	0028-1298
Megjegyzések:	Endothelin-1(ET-1),apotentvasoconstrictornormallyactiveinmaintainingvasculartone,maymediatesignificantpathogeniceffects, contributing to several serious diseases when aberrantly expressed or regulated. The present study evaluates the capacity of ET-1 to affect endothelin-1-associated hypertrophic activity and decreased expression of heme oxygenase-1 by H9c2 rat cardiomyoblasts in vitro, corresponding to in vivo processes underlying cardiovascular diseases (CVDs). Beta estradiol (?-E) is tested for its capacity to altertheeffectsofET-1.H9c2cells,cultured48h,werestimulatedwith100?10,000 nM of ET-1andevaluatedfor changes incell size,cellviability,andexpressionofthecytoprotectiveheatshockproteinhemeoxygenase-1(HO-1),with200nMof?-Eincludedin selectedculturestoevaluateitseffectonET-1-mediatedchanges.Theapplicationof100to10,000nMofET-1resultedinasignificant increase in average cell size and decreases in both cell viability and HO-1 protein content (p<0.05). Moreover, 200 nM of ?-E was observedtosignificantlycounteracttheseeffectsbycardiomyoblastsstimulatedwith1000nMofET-1(p<0.05).Sprague-Dawleyrats treated intravenously with 1000 ng/kg of ET-1 demonstrated reduced HO-1 expression in peripheral blood and left ventricular tissue, whichwascounteractedbyinjectionof200ng/kg?-E?demonstratingapossiblecorrespondencebetweeninvitroandinvivoeffects. Anoutcomeofparticularvalueforclinicaluseof ?-E,inthemanagementofcardiachypertrophy,istheobservedcapacityofthedrug to abate ET-1-mediated suppression of HO-1 expression. It has been previously demonstrated that HO-1 inducers exhibit potent cardioprotective properties, thus offering the promise of combining them with ?-E, allowing lower effective dosage of the drug and concomitantly lower adverse side effects associated with its clinical use. Major findings of this investigation are that pretreatment of cardiomyoblasts with ?-E inhibited their hypertrophic response to ET-1 and counteracts the decrease of cell viability. These effects were associated with a restoration of HO-1 protein expression in both under in vitro and in vivo conditions.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban endothelin H9c2 Beta-estradiol
Megjelenés:	Naunyn-Schmiedebergs Archives Of Pharmacology. - 391 : 4 (2018), p. 371-383. -
További szerzők:	Tósaki Ágnes (1992-) (bőrgyógyász) Haines, David Donald (1981-) (gyógyszerész) Balla György (1953-) (csecsemő és gyermekgyógyász, neonatológus) Lekli István (1981-) (gyógyszerész) Tósaki Árpád (1958-) (kísérletes farmakológus, gyógyszerész)
Pályázati támogatás:	OTKA-104017 OTKA GINOP-2.3.2-15-2016-00043 GINOP K104017 OTKA NKFIH-124719 NKFIH PD-111794 OTKA TÁMOP-4.2.4. A/2-11-1-2012-0001 TÁMOP GINOP-2.3.2-15-2016-00043 GINOP
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