Physiol. Genomics  AJP: Regulatory, Integrative and Comparative Physiology
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Physiol. Genomics (June 3, 2008). doi:10.1152/physiolgenomics.90217.2008
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Submitted on April 11, 2008
Revised on May 26, 2008
Accepted on May 27, 2008

PGC-1{alpha} INCREASES SKELETAL MUSCLE LACTATE UPTAKE BY INCREASING THE EXPRESSION OF MCT1 BUT NOT MCT2 OR MCT4

Carley R Benton, Yuko Yoshida, James Lally, Xiao-Xia Han1, Hideo Hatta2, and Arend Bonen3*

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{alpha}, 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{alpha}, in vivo. Among rat muscles, there was a strong positive association between PGC-1{alpha} and MCT1 and CD147, and between MCT1 and CD147. A negative association was found between PGC-1{alpha} and MCT4, and CD147 and MCT4; there was no relationship between PGC-1 or CD147 and MCT2. Transfecting PGC-1{alpha} into muscle increased PGC-1{alpha} (RTA +23%; WTA +25%) and induced the expression of MCT1 (RTA +16%; WTA +28%), but not MCT2 and MCT4. Along with the PGC-1{alpha}-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{alpha} 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{alpha} transfection and chronic muscle stimulation, there was a strong relationship between the expression of PGC-1{alpha} and MCT1, and PGC-1{alpha} and CD147 proteins. Thus, MCT1 and CD147 belong to the family of metabolic genes whose expression is regulated by PGC-1{alpha} in skeletal muscle.




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