Molecular responses to high-intensity interval exerciseThis paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

2009 ◽  
Vol 34 (3) ◽  
pp. 428-432 ◽  
Author(s):  
Martin Gibala
Keyword(s):  
Protein Kinase ◽  
Endurance Training ◽  
Signaling Pathways ◽  
Mitochondrial Biogenesis ◽  
High Intensity ◽  
Mitogen Activated Protein Kinase ◽  
Interval Exercise ◽  
Mitogen Activated Protein ◽  
High Intensity Interval ◽  
Amp Activated Protein Kinase

From a cell-signaling perspective, short-duration intense muscular work is typically associated with resistance training and linked to pathways that stimulate growth. However, brief repeated sessions of high-intensity interval exercise training (HIT) induce rapid phenotypic changes that resemble traditional endurance training. Given the oxidative phenotype that is rapidly upregulated by HIT, it is plausible that metabolic adaptations to this type of exercise could be mediated in part through signaling pathways normally associated with endurance training. A key controller of oxidative enzyme expression in skeletal muscle is peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcriptional coactivator that serves to coordinate mitochondrial biogenesis. Most studies of acute PGC-1α regulation in humans have used very prolonged exercise interventions; however, it was recently shown that a surprisingly small dose of very intense interval exercise, equivalent to only 2 min of all-out cycling, was sufficient to increase PGC-1α mRNA during recovery. Intense interval exercise has also been shown to acutely increase the activity of signaling pathways linked to PGC-1α and mitochondrial biogenesis, including AMP-activated protein kinase (α1 and α2 subunits) and the p38 mitogen-activated protein kinase. In contrast, signaling pathways linked to muscle growth, including protein kinase B/Akt and downstream targets p70 ribosomal S6 kinase and 4E binding protein 1, are generally unchanged after acute interval exercise. Signaling through AMP-activated protein kinase and p38 mitogen-activated protein kinase to PGC-1α may therefore explain, in part, the metabolic remodeling induced by HIT, including mitochondrial biogenesis and an increased capacity for glucose and fatty acid oxidation.

Carbohydrate feeding during recovery alters the skeletal muscle metabolic response to repeated sessions of high-intensity interval exercise in humans

2010 ◽  
Vol 108 (3) ◽  
pp. 628-636 ◽  
Author(s):  
Andrew J. R. Cochran ◽  
Jonathan P. Little ◽  
Mark A. Tarnopolsky ◽  
Martin J. Gibala
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Exercise Training ◽  
P38 Mapk ◽  
High Intensity ◽  
Metabolic Response ◽  
Training Session ◽  
Mitogen Activated Protein Kinase ◽  
Interval Exercise ◽  
High Intensity Interval

Exercise training under conditions of reduced carbohydrate (CHO) availability has been reported to augment gains in skeletal muscle oxidative capacity; however, the underlying mechanisms are unclear. We examined the effect of manipulating CHO intake on the acute metabolic response to high-intensity interval exercise, including signaling cascades linked to mitochondrial biogenesis. Ten men performed two trials in random order separated by ≥1 wk. Each trial consisted of a morning (AM) and afternoon (PM) training session (5 × 4 min cycling at ∼90–95% of heart rate reserve) separated by 3 h of recovery during which subjects ingested a high-CHO drink (HI-HI) or nonenergetic placebo (HI-LO) before PM exercise. Biopsies (vastus lateralis) revealed that muscle phosphocreatine and ATP content were similar after AM exercise but decreased to a greater extent during PM exercise in HI-LO vs. HI-HI. Phosphorylation of p38 mitogen-activated protein kinase (MAPK) and AMP-activated protein kinase (AMPK) increased ∼4-fold and 2-fold, respectively, during AM exercise with no difference between conditions. After PM exercise, p38 MAPK phosphorylation was higher in HI-LO vs. HI-HI, whereas AMPK was not different between conditions. Peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) gene expression increased ∼8-fold during recovery from AM exercise and remained elevated during PM exercise with no differences between conditions. Cytochrome oxidase subunit 4 (COXIV) mRNA was also elevated 3 h after AM exercise, with no difference between conditions. These data provide evidence that p38 MAPK is a nutrient-sensitive signaling molecule that could be involved in the altered skeletal muscle adaptive response reported after exercise training under conditions of restricted CHO intake, but further research is required to confirm this hypothesis.

scholarly journals Astaxanthin Modulation of Signaling Pathways That Regulate Autophagy

Marine Drugs ◽  
2019 ◽  
Vol 17 (10) ◽  
pp. 546 ◽  
Author(s):  
Suhn Hyung Kim ◽  
Hyeyoung Kim
Keyword(s):  
Protein Kinase ◽  
Cell Survival ◽  
Signaling Pathways ◽  
Experimental Models ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Cellular Homolog ◽  
Cell Components ◽  
Models Of Disease ◽  
Amp Activated Protein Kinase

Autophagy is a lysosomal pathway that degrades and recycles unused or dysfunctional cell components as well as toxic cytosolic materials. Basal autophagy favors cell survival. However, the aberrant regulation of autophagy can promote pathological conditions. The autophagy pathway is regulated by several cell-stress and cell-survival signaling pathways that can be targeted for the purpose of disease control. In experimental models of disease, the carotenoid astaxanthin has been shown to modulate autophagy by regulating signaling pathways, including the AMP-activated protein kinase (AMPK), cellular homolog of murine thymoma virus akt8 oncogene (Akt), and mitogen-activated protein kinase (MAPK), such as c-Jun N-terminal kinase (JNK) and p38. Astaxanthin is a promising therapeutic agent for the treatment of a wide variety of diseases by regulating autophagy.

scholarly journals TRAF6-Dependent Mitogen-Activated Protein Kinase Activation Differentially Regulates the Production of Interleukin-12 by Macrophages in Response to Toxoplasma gondii

2004 ◽  
Vol 72 (10) ◽  
pp. 5662-5667 ◽  
Author(s):  
Nicola J. Mason ◽  
Jim Fiore ◽  
Takashi Kobayashi ◽  
Katherine S. Masek ◽  
Yongwon Choi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Toxoplasma Gondii ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Interleukin 12 ◽  
Wild Type ◽  
Kinase Activation ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

ABSTRACT The production of interleukin-12 (IL-12) is critical to the development of innate and adaptive immune responses required for the control of intracellular pathogens. Many microbial products signal through Toll-like receptors (TLR) and activate NF-κB family members that are required for the production of IL-12. Recent studies suggest that components of the TLR pathway are required for the production of IL-12 in response to the parasite Toxoplasma gondii; however, the production of IL-12 in response to this parasite is independent of NF-κB activation. The adaptor molecule TRAF6 is involved in TLR signaling pathways and associates with serine/threonine kinases involved in the activation of both NF-κB and mitogen-activated protein kinase (MAPK). To elucidate the intracellular signaling pathways involved in the production of IL-12 in response to soluble toxoplasma antigen (STAg), wild-type and TRAF6−/− mice were inoculated with STAg, and the production of IL-12(p40) was determined. TRAF6−/− mice failed to produce IL-12(p40) in response to STAg, and TRAF6−/− macrophages stimulated with STAg also failed to produce IL-12(p40). Studies using Western blot analysis of wild-type and TRAF6−/− macrophages revealed that stimulation with STAg resulted in the rapid TRAF6-dependent phosphorylation of p38 and extracellular signal-related kinase, which differentially regulated the production of IL-12(p40). The studies presented here demonstrate for the first time that the production of IL-12(p40) in response to toxoplasma is dependent upon TRAF6 and p38 MAPK.

scholarly journals Epstein-Barr Virus (EBV) Tegument Protein BGLF2 Promotes EBV Reactivation through Activation of the p38 Mitogen-Activated Protein Kinase

2015 ◽  
Vol 90 (2) ◽  
pp. 1129-1138 ◽  
Author(s):  
XueQiao Liu ◽  
Jeffrey I. Cohen
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Epstein Barr Virus ◽  
Virus Production ◽  
Mitogen Activated Protein Kinase ◽  
Tegument Protein ◽  
Barr Virus ◽  
Ebv Reactivation ◽  
Mitogen Activated Protein ◽  
Epstein Barr

ABSTRACTEpstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus associated with both B cell and epithelial cell malignancies. EBV infection of B cells triggers activation of several signaling pathways that are critical for cell survival, virus latency, and growth transformation. To identify EBV proteins important for regulating cell signaling, we used a proteomic approach to screen viral proteins for AP-1 and NF-κB promoter activity in AP-1– and NF-κB–luciferase reporter assays. We found that EBV BGLF2 activated AP-1 but not NF-κB reporter activity. Expression of EBV BGLF2 in cells activated p38 and c-Jun N-terminal kinase (JNK), both of which are important for mitogen-activated protein kinase (MAPK) signaling. Deletion of the carboxyl-terminal 66 amino acids of BGLF2 reduced the ability of BGLF2 to activate JNK and p38. Expression of BGLF2 enhanced BZLF1 expression in latently EBV-infected lymphoblastoid cell lines, and knockdown of BGLF2 reduced EBV reactivation induced by IgG cross-linking. Expression of BGLF2 induced BZLF1 expression and virus production in EBV-infected gastric carcinoma cells. BGLF2 enhanced BZLF1 expression and EBV production by activating p38; chemical inhibition of p38 and MAPK/ERK kinases 1 and 2 (MEK1/2) reduced expression of BZLF1 and virus production induced by BGLF2. In summary, the EBV tegument protein BGLF2, which is delivered to the cell at the onset of virus infection, activates the AP-1 pathway and enhances EBV reactivation and virus production.IMPORTANCEEpstein-Barr virus (EBV) is associated with both B cell and epithelial cell malignancies, and the virus activates multiple signaling pathways important for its persistence in latently infected cells. We identified a viral tegument protein, BGLF2, which activates members of the mitogen-activated protein kinase signaling pathway. Expression of BGLF2 increased expression of EBV BZLF1, which activates a switch from latent to lytic virus infection, and increased production of EBV. Inhibition of BGFL2 expression or inhibition of p38/MAPK, which is activated by BGLF2, reduced virus reactivation from latency. These results indicate that a viral tegument protein which is delivered to cells upon infection activates signaling pathways to enhance virus production and facilitate virus reactivation from latency.

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