ISSN:
1432-0738
Schlagwort(e):
Organotins
;
45Ca uptake
;
Ca2+-ATPase
;
Protein phosphorylation
;
Heart
;
Sarcoplasmic reticulum-cAMP
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Abstract Organotin compounds have been shown to interfere with cardiovascular system. We have studied the in vitro and in vivo effects of tributyltin bromide (TBT), triethyltin bromide (TET) and trimethyltin chloride (TMT) on the cardiac SR Ca2+ pump, as well as on protein phosphorylation of SR proteins, in order to understand the relative potency of these tin compounds. All the three tin compounds inhibited cardiac SR45Ca uptake and Ca2+-ATPase in vitro in a concentration-dependent manner. The order of potency for Ca2+-ATPase as determined by IC50, is TBT (2 μM) 〉 TET (63 μM) 〉 TMT (280 μM). For45Ca uptake, it followed the same order i.e., TBT (0.35 μM) 〉 TET (10 μM) 〉 TMT (440 μM). In agreement with the in vitro results, both SR Ca2+-ATPase and45Ca uptake were significantly inhibited in rats treated with these tin compounds, indicating that these tin compounds inhibit cardiac SR Ca2+ transport. cAMP significantly elevated (70–80%) the32P-binding to SR proteins in vitro in the absence of any organotin. In the presence of organotins, cAMP-stimulated32P-binding to proteins was significantly reduced, but the decrease was concentration dependent only at lower concentrations. The order of potency is TBT 〉 TET 〉 TMT. In agreement with in vitro studies, cAMP-dependent32P bound to proteins was significantly reduced in rats treated with TBT, TET and TMT. SDS-polyacrylamide gel electrophoresis of the cardiac SR revealed at least 30 Coomassie blue stainable bands ranging from 9 to 120 kDa. Autoradiographs from samples incubated in the presence of cAMP indicated32P incorporation in seven bands. Of these, the band corresponding to about 24 kDa molecular weight protein decreased in its intensity with the treatment of organotins. These results suggest that triorganotins may be affecting Ca2+ pumping mechanisms through the alteration of phosphorylation of specific proteins in rat cardiac SR.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF01968965
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