Monocarboxylate transporter expression in the spontaneous hypertensive rat: Effect of stroke

Abstract

The expression of the monocarboxylate transporters (MCT) 1, 2, and 4 have been studied in the brains of spontaneous hypertensive (SH) rats after an ischemic insult induced by a permanent occlusion of the left middle cerebral artery (MCAO). Profound temporal changes in MCT1 expression were observed in various regions of the ipsilateral hemisphere over the period of 1 hr to 5 days after MCAO. Initially, a very rapid and transient increase in MCT1 mRNA was observed in neurons in the second layer of the cortex and in the piriform cortex at 1-3 hr. A slower but sustained increase in MCT1 mRNA expression was observed in astrocytes in the peri-infarct region beginning at 6 hr after MCAO and persisting over a period of 120 hr coinciding with their activation, migration, and involvement in scar formation. An increase in MCT1 expression in endothelial cells was seen over the same period. These increases in MCT1 expression in astrocytes and endothelial cells were accompanied by a corresponding increase in MCT1 protein. Finally at 120 hr post-MCAO, increases in MCT1, MCT2, and MCT4 expression were observed in cells within the infarct and bordering the scar, the identity of which remains to be determined. Consistent with cell death, the levels of MCT1, MCT2, and MCT4 mRNA decreased with cell death within the infarcted area but unlike MCT1, no increases in either MCT2 or 4 were observed within the remaining ipsilateral hemisphere. These studies reveal that the pattern of regulation of MCT1 expression after MCAO is similar to that observed previously for glucose transporter 1 (GLUT1) and suggest that the regulation of MCT1 mRNA expression is mediated by the hypoxia-inducible transcription factor HIF1.

Clinical and Functional Relevance of the Monocarboxylate Transporter Family in Disease Pathophysiology and Drug Therapy

“…Indeed, decreased lactate content accompanied by reduced MCT2 expression was demonstrated in the cerebral cortex and hippocampus in a rat model of the disease 61. Changes in rat MCT expression were also observed in response to oxygen deprivation, for instance, due to ischemic stroke 62. In contrast, in a mouse model of Parkinson disease, which is also characterized by compromised energy metabolism, no alterations of MCT expression were found 61…”

Diet-induced ketosis increases capillary density without altered blood flow in rat brain

“…MCT-1 and MCT-2 are known to play major functional roles in monocarboxylate metabolism in the brain in nonvascular and vascular regions. For example, MCT expression in rat brain has been associated with a role in the metabolic recovery following an ischemic insult (36,45). However, the molecular and biochemical mechanisms underlying the regulation of MCT proteins in the brain, especially during a chronic state of ketosis, remain to be discerned.…”

Expression of Monocarboxylate Transporter 1 in Oral and Ocular Canine Melanocytic Tumors

“…Several studies have reported that MCT 1 expression was increased when cells became hypoxic because of disease states such as stroke or neoplasia. 7,21,34,42 This study demonstrated that MCT1 was frequently expressed in canine oral melanoma and that there were no statistically significant differences in staining grade between different histologic subtypes. We also obtained an approximately 45-kDa band by Western blotting from 3 oral melanomas, the size of which was consistent with that of canine MCT1 protein detected in control colonic tissue.…”