PMID- 11489783
OWN - NLM
STAT- MEDLINE
DCOM- 20010913
LR  - 20190623
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 104
IP  - 6
DP  - 2001 Aug 7
TI  - Upregulation of the cardiac monocarboxylate transporter MCT1 in a rat model of 
      congestive heart failure.
PG  - 729-34
AB  - BACKGROUND: Cardiac metabolism becomes more dependent on carbohydrates in 
      congestive heart failure (CHF), and lactate may be used as an important 
      respiratory substrate. Monocarboxylate transporter 1 (MCT1) promotes cotransport 
      of lactate and protons into and out of heart cells and conceivably flux of 
      lactate between cells, because it is abundantly present in the intercalated disk. 
      METHODS AND RESULTS: Six weeks after induction of myocardial infarction (MI) in 
      Wistar rats, left ventricular end-diastolic pressures were >15 mm Hg, signifying 
      CHF. MCT1 and connexin43 protein levels in CHF were 260% and 20%, respectively, 
      of those in sham-operated animals (Sham), and the corresponding mRNA signals were 
      181% and not significantly changed, respectively. Confocal laserscan 
      immunohistochemistry and quantitative immunogold cytochemistry showed that MCT1 
      density was much higher in CHF than in Sham both at the surface membrane and in 
      the intercalated disk. In CHF, a novel intracellular pool of MCT1 appeared to be 
      associated with cisternae, some close to the T tubules. In contrast, connexin43 
      particles, seen exclusively at gap junctions, were substantially fewer. Maximum 
      lactate uptake was 107+/-15 mmol. L(-1). min(-1) in CHF and 42+/-6 mmol. L(-1). 
      min(-1) in Sham cells (P<0.05). The K(m) values were between 7 and 9 mmol/L 
      (P=NS). CONCLUSIONS: In cardiomyocytes from CHF rats, (1) the amount of 
      functional MCT1 in the sarcolemma, including in the intercalated disk, is 
      increased several-fold; (2) a new intracellular pool of MCT1 appears; (3) another 
      disk protein, connexin43, is much reduced; and (4) increased reliance on lactate 
      and other monocarboxylates (eg, pyruvate) could provide tight metabolic control 
      of high-energy phosphates.
FAU - Johannsson, E
AU  - Johannsson E
AD  - Department of Anatomy, Institute of Basic Medical Sciences, Institute for 
      Experimental Medical Research, Ullevaal Hospital, University of Oslo, Oslo, 
      Norway.
FAU - Lunde, P K
AU  - Lunde PK
FAU - Heddle, C
AU  - Heddle C
FAU - Sjaastad, I
AU  - Sjaastad I
FAU - Thomas, M J
AU  - Thomas MJ
FAU - Bergersen, L
AU  - Bergersen L
FAU - Halestrap, A P
AU  - Halestrap AP
FAU - Blackstad, T W
AU  - Blackstad TW
FAU - Ottersen, O P
AU  - Ottersen OP
FAU - Sejersted, O M
AU  - Sejersted OM
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Carrier Proteins)
RN  - 0 (Lactates)
RN  - 0 (Monocarboxylic Acid Transporters)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Animals
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Carrier Proteins/genetics/*metabolism
MH  - Disease Models, Animal
MH  - Gene Expression Regulation
MH  - Heart Failure/genetics/*metabolism/physiopathology
MH  - Heart Ventricles/physiopathology
MH  - Lactates/pharmacokinetics
MH  - Microscopy, Confocal
MH  - Microscopy, Electron
MH  - Monocarboxylic Acid Transporters
MH  - Myocardium/*chemistry/pathology/ultrastructure
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Up-Regulation
EDAT- 2001/08/08 10:00
MHDA- 2001/09/14 10:01
CRDT- 2001/08/08 10:00
PHST- 2001/08/08 10:00 [pubmed]
PHST- 2001/09/14 10:01 [medline]
PHST- 2001/08/08 10:00 [entrez]
AID - 10.1161/hc3201.092286 [doi]
PST - ppublish
SO  - Circulation. 2001 Aug 7;104(6):729-34. doi: 10.1161/hc3201.092286.