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J Appl Physiol 92: 1573-1584, 2002. First published January 18, 2002; doi:10.1152/japplphysiol.01069.2001
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Vol. 92, Issue 4, 1573-1584, April 2002

Changes in MCT 1, MCT 4, and LDH expression are tissue specific in rats after long-term hypobaric hypoxia

Grant B. McClelland and George A. Brooks

Exercise Physiology Laboratory, Department of Integrative Biology, University of California, Berkeley, California 94720

Little is known about the effect of chronic hypobaric hypoxia on the enzymes and transporters involved in lactate metabolism. We looked at the protein expression of monocarboxylate transporters MCT 1, MCT 2, and MCT 4, along with total lactate dehydrogenase (LDH) and LDH isozymes in skeletal muscle, cardiac muscle, and liver. Expression of these components of the lactate shuttle affects the ability to transport and oxidize lactate. We hypothesized that the expression of MCTs and LDH would increase after acclimation to high altitude (HA). The response to acclimation to HA was, however, tissue specific. In addition, the response was different in whole muscle (Mu) and mitochondria-enriched (Mi) fractions. Heart, soleus, and plantaris muscles showed the greatest response to HA. Acclimation resulted in a 34% increase in MCT 4 in heart and a decrease in MCT 1 (-47%) and MCT 4 (-47%) in plantaris Mu. In Mi fractions, the heart had an increase (+40%) and soleus a decrease (-40%) in LDH. HA also had a significant effect on the LDH isozyme composition of both the Mu and Mi fractions. Mitochondrial density was decreased in both the soleus (-17%) and plantaris (-44%) as a result of chronic hypoxia. We conclude that chronic hypoxia had a tissue-specific effect on MCTs and LDH (that form the lactate shuttle) but did not produce a consistent increase in these components in all tissues.

monocarboxylate transporters; lactate dehydrogenase isozymes; lactate shuttle; lactate metabolism; high-altitude acclimation; cytochrome oxidase


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