Antidigoxin antiserum prevents endogenous digitalis-like compound-mediated reperfusion injury via modulating sodium pump isoform gene expression.
Endogenous digitalis-like compound (EDLC) is an endogenous ligand of the digitalis receptor and can remarkably inhibit Na+/K+-ATPase activity. Antidigoxin antiserum (ADA), a selective EDLC antagonist, may lessen myocardial reperfusion injury; however, the molecular mechanisms underlying the effect remain unclear. Therefore, this study investigated whether ADA may prevent myocardial reperfusion injury and modulate gene expression of sodium pump alpha isoforms. Cardiac function was examined in isolated rat hearts subjected to ischemia and reperfusion (I/R). The infarct size, EDLC level, Na+/K+-ATPase activity, and the levels of mRNA for sodium pump alpha isoforms were measured in vivo I/R rat hearts in the presence or absence of ADA. It was found that ADA significantly improved the recovery of cardiac function, decreased infarct size, decreased EDLC level, and recovered Na+/K+-ATPase activity in I/R hearts. Further studies showed that sodium pump alpha1, alpha2, and alpha3 isoform mRNA levels were significantly reduced in I/R hearts, and pretreatment with ADA induced a large increase in the mRNA levels. These results indicate that EDLC may participate in depressing Na+/K+-ATPase activity and sodium pump alpha isoform gene expression in I/R heart. It is suggested that treatment with ADA may prevent EDLC-mediated reperfusion injury via modulating sodium pump isoform gene expression.
Department of Cardiology, Yijishan Hospital, Wannan Medical College, Wuhu 241001, China.
He-Gui
HG
Wang
Yue-Feng
YF
Chu
Jian-Gang
JG
Zou
Yong-Sheng
YS
Ke
D000818:Animals; D002298:Cardenolides / Q000633:toxicity*; D004077:Digoxin / Q000037:antagonists & inhibitors* / Q000276:immunology; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D007106:Immune Sera / Q000008:administration & dosage*; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000633:toxicity*; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis* / Q000235:genetics
D002298:Cardenolides; D007106:Immune Sera; D007527:Isoenzymes; D012503:Saponins; C034504:digoxin-like factors; D004077:Digoxin; C499075:Atp1a1 protein, rat; D000254:Sodium-Potassium-Exchanging ATPase