Increased expression of monocarboxylate transporter 1 after acute ischemia of isolated, perfused mouse hearts.
OBJECTIVE
Lactate is transported by stereo-specific, pH-dependent monocarboxylate transporters (MCTs), of which MCT1 is expressed in abundance in rodent and human hearts. This study investigated the expression and functional role of MCT1 in mouse hearts during acute myocardial ischemia.


METHODS
Mice hearts were isolated and Langendorff-perfused with induced global ischemia (40 min) and reperfusion with function and infarct size as end-points. Hearts were collected serially for protein extraction and immunoblotting with an MCT1 antibody, and for determining subcellular localization with immunogold EM. Immortalized cardiomyocytes (HL-1 cells) were injured with hydrogen peroxide, and cell death in the presence or absence of the competitive inhibitor of MCT1, d-lactate, was evaluated by Trypan blue exclusion.


RESULTS
MCT1 expression increased after 15 min reperfusion (p<0.05), but was not significantly increased after 60 min. MCT1 was localized in mitochondria, plasma membrane, and intercalated disks. At 15 min reperfusion, gold particle count was increased in the intercalated disks (p<0.05). d-lactate administration to isolated hearts either for 5 min before ischemia or at the first 5 min of reperfusion increased infarct size (p<0.01). A significant impairment of left ventricular performance was found when d-lactate was given before ischemia. MCT1 expression was not influenced by d-lactate. When HL-1 cells were treated with d-lactate before injury was induced with hydrogen peroxide, cell death was increased (p<0.05).


CONCLUSIONS
Inhibition of MCT1 increases cell death. Increased MCT1 expression after ischemia and reperfusion is likely to restore cardiac pH through lactate export.
Martinov
Vladimir
V
Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
Rizvi
Syed Mohammad Husain
SM
Weiseth
Stian Andre
SA
Sagave
Julia
J
Bergersen
Linda H
LH
Valen
Guro
G
D000818:Animals; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D051379:Mice; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D009924:Organ Culture Techniques; D021381:Protein Transport; D015424:Reperfusion; D027981:Symporters / Q000378:metabolism*; D000099233:Monocarboxylate Transport Protein 1
D027501:Monocarboxylic Acid Transporters; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1