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INCREASES SKELETAL MUSCLE LACTATE UPTAKE BY INCREASING THE EXPRESSION OF MCT1 BUT NOT MCT2 OR MCT4
1 U of Guelph
2 University of Tokyo
3 University of Guelph
* To whom correspondence should be addressed. E-mail: abonen{at}uoguelph.ca.
We examined the relationship between PGC-1
, the monocarboxylate transporters MCT1, 2 and 4, and CD147, a) among metabolically heterogeneous rat muscles, b) in chronically stimulated red (RTA) and white tibialis (WTA) muscles (7-days), and c) in RTA and WTA transfected with PGC-1
, in vivo. Among rat muscles, there was a strong positive association between PGC-1
and MCT1 and CD147, and between MCT1 and CD147. A negative association was found between PGC-1
and MCT4, and CD147 and MCT4; there was no relationship between PGC-1 or CD147 and MCT2. Transfecting PGC-1
into muscle increased PGC-1
(RTA +23%; WTA +25%) and induced the expression of MCT1 (RTA +16%; WTA +28%), but not MCT2 and MCT4. Along with the PGC-1
-induced upregulation of MCT1, and its chaperone CD147 (+29%), there was a concomitant increase in the rate of lactate uptake (+20%). In chronically stimulated muscles, the following proteins were upregulated, PGC-1
in RTA (+26%) and WTA (+86%), MCT1 in RTA (+61%) and WTA (+180%), and CD147 in WTA (+106%). In contrast, MCT4 protein expression was not altered in either RTA or WTA muscles, while MCT2 protein expression was reduced in both RTA (-14%) and WTA (-10%). In these studies, whether comparing oxidative capacities among muscles, or increasing their oxidative capacities by PGC-1
transfection and chronic muscle stimulation, there was a strong relationship between the expression of PGC-1
and MCT1, and PGC-1
and CD147 proteins. Thus, MCT1 and CD147 belong to the family of metabolic genes whose expression is regulated by PGC-1
in skeletal muscle.
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