Lactate Up-Regulates the Expression of Lactate Oxidation Complex-Related Genes in Left Ventricular Cardiac Tissue of Rats

Gabriel-Costa, Daniele; Cunha, Telma F.; Bechara, Luiz R. G.; Fortunato, Rodrigo S.; Bozi, Luíz Henrique Marchesi; Coelho, Marcele A.; Barreto‐Chaves, Maria Luíza Morais; Brum, Patrícia Chakur

doi:10.1371/journal.pone.0127843

Cited by 15 publications

(22 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Montoya et al (7) showed that it caused vasodilation in isolated aortic rings and coronary arteries in a nitric oxide (NO)-dependent manner. We have also observed that lactate perfusion reduces cardiac perfusion pressure in healthy isolated hearts (5). …”

Section: Introductionmentioning

confidence: 81%

“…Therefore, the aim of the present work was to investigate the effect of lactate perfusion in isolated hearts submitted to chronic experimental MI. We hypothesized that lactate would increase LOC-related gene expression and decrease cardiac perfusion pressure as observed previously in non-ischemic hearts (5). …”

Section: Introductionmentioning

confidence: 89%

“…The heart is an important lactate consumer especially during physiological stress conditions such as exercise (2 –4). We and others have demonstrated that lactate modulates the expression of lactate oxidation complex (LOC)-related genes in both cardiac and skeletal muscle cells, which drive its usage as substrate fuel (5,6). Lactate modulation of LOC-related genes occurs through the activation of redox-sensitive signaling pathways since lactate increases reactive oxygen species (ROS) levels and nuclear expression of the nuclear factor erythroid 2-related factor 2 (NRF-2), a redox-sensitive transcription factor (5,6).…”

Section: Introductionmentioning

confidence: 99%

“…We and others have demonstrated that lactate modulates the expression of lactate oxidation complex (LOC)-related genes in both cardiac and skeletal muscle cells, which drive its usage as substrate fuel (5,6). Lactate modulation of LOC-related genes occurs through the activation of redox-sensitive signaling pathways since lactate increases reactive oxygen species (ROS) levels and nuclear expression of the nuclear factor erythroid 2-related factor 2 (NRF-2), a redox-sensitive transcription factor (5,6). In fact, lactate modulates redox homeostasis in cardiac tissue by increasing the levels of reduced β-nicotinamide adenine dinucleotide (NADH) mainly due to the conversion of lactate to pyruvate by lactate dehydrogenase (LDH), which further activates a specific oxidase (NADH oxidase, NADox) leading to ROS production.…”

Section: Introductionmentioning

confidence: 99%

“…Many studies have demonstrated that oxidation of carbohydrates and other glycolytic substrates improve cardiac performance efficiency, resulting in enhanced heart contractility and less O 2 utilization (8,9). Taking into consideration data from healthy hearts, which demonstrate that lactate up-regulates the expression of LOC-related genes and increases coronary artery blood flux (5), we can hypothesize that it may also influence the establishment of HF. However, to our knowledge, no other study has previously investigated this hypothesis.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Lactate-upregulation of lactate oxidation complex-related genes is blunted in left ventricle of myocardial infarcted rats

Gabriel-Costa

Cunha

Paixão

et al. 2018

Braz J Med Biol Res

View full text Add to dashboard Cite

Lactate modulates the expression of lactate oxidation complex (LOC)-related genes and cardiac blood flow under physiological conditions, but its modulatory role remains to be elucidated regarding pathological cardiac stress. The present study evaluated the effect of lactate on LOC-related genes expression and hemodynamics of hearts submitted to myocardial infarction (MI). Four weeks after MI or sham operation, isolated hearts of male Wistar rats were perfused for 60 min with Na+-lactate (20 mM). As expected, MI reduced cardiac contractility and relaxation with no changes in perfusion. The impaired cardiac hemodynamics were associated with increased reactive oxygen species (ROS) levels (Sham: 19.3±0.5 vs MI: 23.8±0.3 µM), NADPH oxidase (NOX) activity (Sham: 42.2±1.3 vs MI: 60.5±1.5 nmol·h−1·mg−1) and monocarboxylate transporter 1 (mct1) mRNA levels (Sham: 1.0±0.06 vs MI: 1.7±0.2 a.u.), but no changes in superoxide dismutase (SOD), catalase, NADH oxidase (NADox), and xanthine oxidase activities. Lactate perfusion in MI hearts had no additional effect on ROS levels, NADox, and NOX activity, however, it partially reduced mct1 mRNA expression (MI-Lactate 1.3±0.08 a.u.). Interestingly, lactate significantly decreased SOD (MI-Lactate: 54.5±4.2 µmol·mg−1·min−1) and catalase (MI: 1.1±0.1 nmol·mg−1·min−1) activities in MI. Collectively, our data suggest that under pathological stress, lactate lacks its ability to modulate the expression of cardiac LOC-related genes and the perfused pressure in hearts submitted to chronic MI. Together, these data contribute to elucidate the mechanisms involved in the pathogenesis of heart failure induced by MI.

show abstract

Section: Introductionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Lactate-upregulation of lactate oxidation complex-related genes is blunted in left ventricle of myocardial infarcted rats

Gabriel-Costa

Cunha

Paixão

et al. 2018

Braz J Med Biol Res

View full text Add to dashboard Cite

show abstract

Molecular changes in mitochondrial respiratory activity and metabolic enzyme activity in muscle of four pig breeds with distinct metabolic types

Trakooljul

Muráni

et al. 2016

J Bioenerg Biomembr

View full text Add to dashboard Cite

Skeletal muscles are metabolically active and have market value in meat-producing farm animals. A better understanding of biological pathways affecting energy metabolism in skeletal muscle could advance the science of skeletal muscle. In this study, comparative pathway-focused gene expression profiling in conjunction with muscle fiber typing were analyzed in skeletal muscles from Duroc, Pietrain, and Duroc-Pietrain crossbred pigs. Each breed type displayed a distinct muscle fiber-type composition. Mitochondrial respiratory activity and glycolytic and oxidative enzyme activities were comparable among genotypes, except for significantly lower complex I activity in Pietrain pigs homozygous-positive for malignant hyperthermia syndrome. At the transcriptional level, lactate dehydrogenase B showed breed specificity, with significantly lower expression in Pietrain pigs homozygous-positive for malignant hyperthermia syndrome. A similar mRNA expression pattern was shown for several subunits of oxidative phosphorylation complexes, including complex I, complex II, complex IV, and ATP synthase. Significant correlations were observed between mRNA expression of genes in focused pathways and enzyme activities in a breed-dependent manner. Moreover, expression patterns of pathway-focused genes were well correlated with muscle fiber-type composition. These results stress the importance of regulation of transcriptional rate of genes related to oxidative and glycolytic pathways in the metabolic capacity of muscle fibers. Overall, the results further the breed-specific understanding of the molecular basis of metabolic enzyme activities, which directly impact meat quality.

show abstract

Lactate regulates autophagy through ROS-mediated activation of ERK1/2/m-TOR/p-70S6K pathway in skeletal muscle

Nikooie

Moflehi

Zand

2021

J. Cell Commun. Signal.

View full text Add to dashboard Cite

The role of autophagy and lysosomal degradation pathway in the regulation of skeletal muscle metabolism was previously studied. However, underlying molecular mechanisms are poorly understood. L‐lactate which is utilized as an energetic substrate by skeletal muscle can also augment genes expression related to metabolism and up‐regulate those being responsive to reactive oxygen species (ROS). Since ROS is the most important regulator of autophagy in skeletal muscle, we tested if there is a link between cellular lactate metabolism and autophagy in differentiated C2C12 myotubes and the gastrocnemius muscle of male wistar rats. C2C12 mouse skeletal muscle was exposed to 2, 6, 10, and 20 mM lactate and evaluated for lactate autophagic effects. Lactate dose‐dependently increased autophagy and augmented ROS generation in differentiated C2C12 myotubes. The autophagic effect of lactate deterred in N‐acetylcysteine presence (NAC, a ROS scavenger) indicated lactate regulates autophagy with ROS participation. Lactate‐induced up‐regulation of extracellular signal‐regulated kinase 1/2 (ERK1/2) through ROS was required to regulate the autophagy by lactate. Further analysis about ERK1/2 up‐ and downstream indicated that lactate regulates autophagy through ROS‐mediated the activation of ERK1/2/mTOR/p70S6K pathway in skeletal muscle. The in vitro effects of lactate on autophagy also occurred in the gastrocnemius muscle of male Wistar rats. In conclusion, we provided the lactate‐associated regulation evidence of autophagy in skeletal muscle by activating ROS‐mediated ERK1/2/mTOR/p70S6K pathway. Since the increase in cellular lactate concentration is a hallmark of energy deficiency, the results provide insight into a skeletal muscle mechanism to fulfill its enhanced energy requirement.

show abstract

Lactate Up-Regulates the Expression of Lactate Oxidation Complex-Related Genes in Left Ventricular Cardiac Tissue of Rats

Cited by 15 publications

References 44 publications

Lactate-upregulation of lactate oxidation complex-related genes is blunted in left ventricle of myocardial infarcted rats

Lactate-upregulation of lactate oxidation complex-related genes is blunted in left ventricle of myocardial infarcted rats

Molecular changes in mitochondrial respiratory activity and metabolic enzyme activity in muscle of four pig breeds with distinct metabolic types

Lactate regulates autophagy through ROS-mediated activation of ERK1/2/m-TOR/p-70S6K pathway in skeletal muscle

Contact Info

Product

Resources

About