A halocin acting on Na+/H+ exchanger of haloarchaea as a new type of inhibitor in NHE of mammals.
The capability of halocin H6 (a bacteriocin-like protein produced by haloarchaea Haloferax gibbonsii) to inhibit Na+/H+ exchanger (NHE) in mammalian cells and its cardio-protective efficacy on the ischemic and reperfused myocardium were evaluated in the present study. H6 inhibits NHE activity (measured by a flow cytometry method) in a dose-dependent form of cell lines of mammalian origin (HEK293, NIH3T3, Jurkat and HL-1) as well as in primary cell culture from human skeletal muscle (myocytes and fibroblasts). In vivo, an ischemia-reperfusion model in dogs by coronary arterial occlusion was used (two hours of regional ischemia and three hours of reperfusion). In animals treated with halocin H6 there was a significant reduction of premature ventricular ectopic beats and infarct size, whereas blood pressure and heart rate remained unchanged. Up to date, halocin H6 is the only described biological molecule that exerts a specific inhibitory activity in NHE of eukaryotic cells.
Lequerica
J L
JL
Instituto de Biomedicina, Spanish Council for Scientific Research CSIC, Valencia. jlequerica@ibv.csic.es
O'Connor
J E
JE
Such
L
L
Alberola
A
A
Meseguer
I
I
Dolz
M
M
Torreblanca
M
M
Moya
A
A
Colom
F
F
Soria
B
B
D000818:Animals; D001105:Archaea / Q000737:chemistry*; D001430:Bacteriocins / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D051379:Mice; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*
D001430:Bacteriocins; D017923:Sodium-Hydrogen Exchangers