Inhibition of calcineurin increases monocarboxylate transporters 1 and 4 protein and glycolytic enzyme activities in rat soleus muscle

Suwa, Masataka; Nakano, Hiroshi; Kumagai, Shuzo

doi:10.1111/j.1440-1681.2005.04176.x

Cited by 5 publications

(2 citation statements)

References 43 publications

(50 reference statements)

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“…Indeed, the serine/threonine phosphatase calcineurin plays a functional role in the hypertrophy and regeneration of skeletal muscle (134). It has been reported that a specific inhibitor of calcineurin by the administration of cyclosporine A increased MCT1 and MCT4 contents only in rat oxidative muscles, which suggests that calcineurin negatively regulates MCT contents with a fiber specificity (142).…”

Section: Which Cellular and Molecular Signals/mechanisms Regulate Musmentioning

confidence: 99%

Effects of acute and chronic exercise on sarcolemmal MCT1 and MCT4 contents in human skeletal muscles: current status

Thomas

Bishop

Lambert

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Two lactate/proton cotransporter isoforms (monocarboxylate transporters, MCT1 and MCT4) are present in the plasma (sarcolemmal) membranes of skeletal muscle. Both isoforms are symports and are involved in both muscle pH and lactate regulation. Accordingly, sarcolemmal MCT isoform expression may play an important role in exercise performance. Acute exercise alters human MCT content, within the first 24 h from the onset of exercise. The regulation of MCT protein expression is complex after acute exercise, since there is not a simple concordance between changes in mRNA abundance and protein levels. In general, exercise produces greater increases in MCT1 than in MCT4 content. Chronic exercise also affects MCT1 and MCT4 content, regardless of the initial fitness of subjects. On the basis of cross-sectional studies, intensity would appear to be the most important factor regulating exercise-induced changes in MCT content. Regulation of skeletal muscle MCT1 and MCT4 content by a variety of stimuli inducing an elevation of lactate level (exercise, hypoxia, nutrition, metabolic perturbations) has been demonstrated. Dissociation between the regulation of MCT content and lactate transport activity has been reported in a number of studies, and changes in MCT content are more common in response to contractile activity, whereas changes in lactate transport capacity typically occur in response to changes in metabolic pathways. Muscle MCT expression is involved in, but is not the sole determinant of, muscle H(+) and lactate anion exchange during physical activity.

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Section: Which Cellular and Molecular Signals/mechanisms Regulate Musmentioning

confidence: 99%

Effects of acute and chronic exercise on sarcolemmal MCT1 and MCT4 contents in human skeletal muscles: current status

Thomas

Bishop

Lambert

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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“…The same group described organ‐specific response to inhibition of mitochondrial metabolism by CSA in the rat (20). Furthermore, CSA treatment activated HK, pyruvatekinase (PK) and LDH in the soleus muscle of rats as a compensatory mechanism for compromised oxidative phosphorylation (72).…”

Section: Discussionmentioning

confidence: 99%

Cyclosporine A: impact on mitochondrial function in endothelial cells

Illsinger

Janzen

Lücke

et al. 2011

Clinical Transplantation

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Cyclosporine protects from intestinal epithelial injury by modulating butyrate uptake via upregulation of membrane monocarboxylate transporter 1 levels

Ota

Sakuraba

Hiraga

et al. 2020

Biochemistry and Biophysics Reports

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Background and aims A relationship between treatment outcomes and intestinal microbiota in patients with inflammatory bowel diseases has been demonstrated. Cyclosporine treatment leads to rapid improvement in severe ulcerative colitis. We hypothesized that the potent effects of cyclosporine would be exerted through relationships between intestinal epithelial cells (IECs) and the host microbiota. The present study was designed to elucidate the effects of cyclosporine on monocarboxylate transporter 1 (MCT1) regulation and butyrate uptake by IECs. Methods Colitis was induced in C57BL6 mice via the administration of 4% dextran sulfate sodium in drinking water, following which body weights, colon lengths, and histological scores were evaluated. To examine the role of butyrate in the protective effects of cyclosporine, MCT1 inhibitor and an antibiotic cocktail was administered and tributyrin (TB; a prodrug of butyrate) was supplemented; MCT1 protein expression and acetylated histone 3 (AcH3) signals in IECs, as well as the MCT1-membrane fraction of Caco-2 cells, were evaluated. To explore butyrate uptake, as s butyrate derivatives, 3-bromopyruvic acid (3-BrPA) and 1-pyrenebutyric acid were used. Results Treatment with cyclosporine inhibited body weight loss and colon length shortening. However, treatment with MCT1 inhibitor and the antibiotic cocktail negated the efficacy of cyclosporine, whereas TB supplementation restored its protective effect. Furthermore, cyclosporine upregulated MCT1 expression in the membrane and the AcH3 signal in IECs, while also inducing higher anti-inflammatory cytokine production compared to that in the vehicle-treated mice. The transcription level of MCT1 mRNA in IECs and Caco-2 cells did not increase with cyclosporine treatment; however, cyclosporine treatment increased membrane MCT1 expression in these cells and uptake of butyrate derivative. Conclusion Cyclosporine treatment modulates butyrate uptake via the post-transcriptional upregulation of membrane MCT1 levels in IECs.

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Inhibition of calcineurin increases monocarboxylate transporters 1 and 4 protein and glycolytic enzyme activities in rat soleus muscle

Cited by 5 publications

References 43 publications

Effects of acute and chronic exercise on sarcolemmal MCT1 and MCT4 contents in human skeletal muscles: current status

Effects of acute and chronic exercise on sarcolemmal MCT1 and MCT4 contents in human skeletal muscles: current status

Cyclosporine A: impact on mitochondrial function in endothelial cells

Cyclosporine protects from intestinal epithelial injury by modulating butyrate uptake via upregulation of membrane monocarboxylate transporter 1 levels

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