MetGeneConjugation - Revision history

Avertyshev@mail.ru: /* Phenotype-Signaling Feedback */

2018-10-15T15:28:44Z

‎Phenotype-Signaling Feedback

Avertyshev@mail.ru at 15:27, 15 October 2018

2018-10-15T15:27:31Z

Avertyshev@mail.ru at 13:43, 4 October 2018

2018-10-04T13:43:39Z

Avertyshev@mail.ru: /* Summary remarks */

2018-10-04T13:40:43Z

‎Summary remarks

Avertyshev@mail.ru: /* Summary remarks */

2018-10-04T13:39:32Z

‎Summary remarks

Avertyshev@mail.ru: /* Summary remarks */

2018-10-04T13:39:02Z

‎Summary remarks

Avertyshev@mail.ru: /* Summary remarks */

2018-10-04T13:35:49Z

‎Summary remarks

Avertyshev@mail.ru at 13:34, 4 October 2018

2018-10-04T13:34:15Z

Avertyshev@mail.ru at 13:28, 4 October 2018

2018-10-04T13:28:36Z

Avertyshev@mail.ru: /* Summary remarks */

2018-10-03T14:56:56Z

‎Summary remarks

← Older revision		Revision as of 15:28, 15 October 2018
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−	[[File: P38_MAPK_phosphorylation_(Yu_2003).png \| ~~600px~~ \| p38 MAPK phosphorylation]]	+	[[File: P38_MAPK_phosphorylation_(Yu_2003).png \| 500px \| p38 MAPK phosphorylation]]


−	[[File: AMPK_activity_and_phosphorylation_(Yu_2003).png \| ~~600px~~ \| AMPK activity and phosphorylation]]	+	[[File: AMPK_activity_and_phosphorylation_(Yu_2003).png \| 500px \| AMPK activity and phosphorylation]]

@@ Line 1: / Line 1: @@
-Points of conjugation between metabolic processes associated with aerobic exercise and regulation of gene expression. Ver. 0.8.
+Points of conjugation between metabolic processes associated with aerobic exercise and regulation of gene expression. Ver. 1.0.
 ===Summary remarks===
@@ Line 48: / Line 48: @@
 Figure 3. (Kjøbsted 2018) <cite>3</cite>.  Activation of different AMPK complexes in skeletal muscle is dependent on exercise intensity and duration. In skeletal muscle, LKB1 is the major upstream kinase responsible for the phosphorylation of α2-containing AMPK complexes in response to high/moderate-intensity and short/limited-duration exercise. In contrast, CaMKKβ phosphorylates and activates α1- containing AMPK complexes during long-term exercise at a low intensity. In human vastus lateralis muscle, AMPK activation is restricted to α2β2γ3 heterotrimers during short (up to 20 min) and intense exercise, whereas the α2β2γ1 and α1β2γ1 complexes appear unchanged or even show decreased activation. When exercise is prolonged, α2β2γ1 heterotrimers are activated. During lower-intensity exercise of longer duration, α2β2γ1 and α1β2γ1  complexes are moderately activated. Thus, in skeletal muscle each AMPK heterotrimer combination is regulated in a distinct manner during contraction depending on exercise intensity and duration, which causes a differential functional response.
 Therefore, AMPK signaling pathway associated with CaMKKβ was excluded from consideration at the first stage of modeling, in accordance with our experimental data.
 The extended data for AMPK, LKB1 and CaMKKβ  in modeling context are present at next Wiki pages: [[AMPK]],  [[LKB1]], [[CaMKKβ]]
 The review of the skeletal muscle metabolism models is present at next Wiki page: [[Muscle_models]]
 === Phenotype-Signaling Feedback===
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 The chronic contractile activity, in the form of repeated bouts of endurance exercise, results in the altered expression of a wide variety of gene products, leading to an altered muscle phenotype with improved fatigue resistance. This improved endurance is highly correlated with the increase in muscle mitochondrial density and enzyme activity, referred to as ‘mitochondrial biogenesis’ (Adhihetty et al., 2003) <cite>4</cite>.
-The improved endurance, the increase in muscle mitochondrial density and the changes in abundance of variety signal proteins, results in the altered signaling pathways activity. For example, contraction-induced AMPKα  phosphorylation was blunted in muscle, in which the oxidative capacity had been enhanced (Ljubicic 2009) <cite>7</cite>,  inverse relationships were observed between mitochondrial volume and some kinase proteins content and their basal levels of phosphorylation. Thus, mitochondrial content and oxidative capacity are determinants of the activation of signaling proteins important to muscle plasticity. The attenuation of kinase phosphorylation in muscle with high mitochondrial content suggests that these proteins may require a greater stimulus input for activation to propagate these cues downstream to evoke phenotypic adaptations.
+The improved endurance, the increase in muscle mitochondrial density and the changes in abundance of variety signal proteins, results in the altered signaling pathways activity. For example, contraction-induced AMPKα  phosphorylation was blunted in mouse skeletal muscle, in which the oxidative capacity had been enhanced (Ljubicic 2009) <cite>7</cite>,  inverse relationships were observed between mitochondrial volume and some kinase proteins content and their basal levels of phosphorylation. Thus, mitochondrial content and oxidative capacity are determinants of the activation of signaling proteins important to muscle plasticity. The attenuation of kinase phosphorylation in muscle with high mitochondrial content suggests that these proteins may require a greater stimulus input for activation to propagate these cues downstream to evoke phenotypic adaptations.
 The Phenotype-Signaling Feedback is intriguing feature for modeling of the long-term adaptation.
@@ Line 75: / Line 83: @@
 #6 pmid=17609368	<!-- Jäger ‎2007 -->
 #7 pmid=19549794	 <!-- Ljubicic 2009 -->
 </biblio>
 [[Category: Human_muscle]]
 [[Category: Signaling Overview]]

← Older revision		Revision as of 13:43, 4 October 2018
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−	Points of conjugation between metabolic processes associated with aerobic exercise and regulation of gene expression. Ver. 0.5.	+	Points of conjugation between metabolic processes associated with aerobic exercise and regulation of gene expression. Ver. 0.8.

	===Summary remarks===		===Summary remarks===

← Older revision		Revision as of 13:40, 4 October 2018
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	The extended data for AMPK, LKB1 and CaMKKβ in modeling context are present at next Wiki pages: [[AMPK]], [[LKB1]], [[CaMKKβ]]		The extended data for AMPK, LKB1 and CaMKKβ in modeling context are present at next Wiki pages: [[AMPK]], [[LKB1]], [[CaMKKβ]]
−

	The review of the skeletal muscle metabolism models is present at next Wiki page: [[Muscle_models]]		The review of the skeletal muscle metabolism models is present at next Wiki page: [[Muscle_models]]

← Older revision		Revision as of 13:39, 4 October 2018
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	Figure 3. (Kjøbsted 2018) <cite>3</cite>. Activation of different AMPK complexes in skeletal muscle is dependent on exercise intensity and duration. In skeletal muscle, LKB1 is the major upstream kinase responsible for the phosphorylation of α2-containing AMPK complexes in response to high/moderate-intensity and short/limited-duration exercise. In contrast, CaMKKβ phosphorylates and activates α1- containing AMPK complexes during long-term exercise at a low intensity. In human vastus lateralis muscle, AMPK activation is restricted to α2β2γ3 heterotrimers during short (up to 20 min) and intense exercise, whereas the α2β2γ1 and α1β2γ1 complexes appear unchanged or even show decreased activation. When exercise is prolonged, α2β2γ1 heterotrimers are activated. During lower-intensity exercise of longer duration, α2β2γ1 and α1β2γ1 complexes are moderately activated. Thus, in skeletal muscle each AMPK heterotrimer combination is regulated in a distinct manner during contraction depending on exercise intensity and duration, which causes a differential functional response.		Figure 3. (Kjøbsted 2018) <cite>3</cite>. Activation of different AMPK complexes in skeletal muscle is dependent on exercise intensity and duration. In skeletal muscle, LKB1 is the major upstream kinase responsible for the phosphorylation of α2-containing AMPK complexes in response to high/moderate-intensity and short/limited-duration exercise. In contrast, CaMKKβ phosphorylates and activates α1- containing AMPK complexes during long-term exercise at a low intensity. In human vastus lateralis muscle, AMPK activation is restricted to α2β2γ3 heterotrimers during short (up to 20 min) and intense exercise, whereas the α2β2γ1 and α1β2γ1 complexes appear unchanged or even show decreased activation. When exercise is prolonged, α2β2γ1 heterotrimers are activated. During lower-intensity exercise of longer duration, α2β2γ1 and α1β2γ1 complexes are moderately activated. Thus, in skeletal muscle each AMPK heterotrimer combination is regulated in a distinct manner during contraction depending on exercise intensity and duration, which causes a differential functional response.
		+

	Therefore, AMPK signaling pathway associated with CaMKKβ was excluded from consideration at the first stage of modeling, in accordance with our experimental data.		Therefore, AMPK signaling pathway associated with CaMKKβ was excluded from consideration at the first stage of modeling, in accordance with our experimental data.

@@ Line 52: / Line 52: @@
 The extended data for AMPK, LKB1 and CaMKKβ  in modeling context are present at next Wiki pages:
-The models are present at next Wiki page:
+[[AMPK]],  [[LKB1]], [[CaMKK𝜷]]
-http://virtualbiology.biouml.org/index.php/Muscle_models

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 ''' Signal transduction pathways in skeletal muscle '''
-The exercise induced adaptation in skeletal muscle involves a multitude of signalling mechanisms. The process of converting a mechanical signal generated during contraction to a molecular event that promotes adaptation in a muscle cell involves the upregulation of primary and secondary messengers that initiate a cascade of events that result in activation and/or repression of specific signalling pathways regulating exercise-induced gene expression and protein synthesis/degradation. Elucidation of the precise mechanisms that enable skeletal muscle cells to interpret and respond to contraction has proved elusive. Nevertheless, there are numerous putative messengers emerging, including, but not limited to, mechanical stretch, calcium flux, redox state and phosphorylation state, see review (Coffey and Hawley 2007) <cite>1</cite>.
 Putative Primary Messengers
@@ Line 13: / Line 14: @@
 * Redox Potential
 * Phosphorylation Potential
+It is unlikely that these primary signalling messengers act in isolation, and probably results in an intricate multifaceted signal with redundancy and cross-talk.
 Secondary Messengers
 * Adenosine Monophosphate Activated Protein Kinase-Mediated Signalling
@@ Line 26: / Line 28: @@
 The most simplified general view on pathways associated with aerobic exercise is presented on figure:
 [[File: Simplified_model_of_the_AMPK_and_CaMK_signaling_pathways_(Laursen_2010).png | 569px | Simplified model of AMPK and CaMK signaling pathways]]
-Fig. 2. (Laursen 2010)  <cite>2</cite>.  Simplified model of the adenosine monophosphate kinase (AMPK) and calcium–calmodulin kinase (CaMK) signaling pathways, as well as their similar downstream target, the peroxisome proliferator-activated receptor-g coactivator-1a (PGC-1a).
+Fig. 2. (Laursen 2010)  <cite>2</cite>.  Simplified model of the adenosine monophosphate kinase (AMPK) and calcium–calmodulin kinase (CaMK) signaling pathways, as well as their similar downstream target, the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α).
 For moderate and high intencity interval aerobic exercise (50-100% of anaerobic threshold, 60 minutes) the CAMK pathway is not significant pathway. Therefore, only AMPK signaling pathway was used at the first stage of modeling.
@@ Line 37: / Line 45: @@
 [[File: Activation_of_different_AMPK_complexes_in_skeletal_muscle_(Kjobsted_2018).png | 800px | Activation of different AMPK complexes in skeletal muscle]]
 Figure 3. (Kjøbsted 2018) <cite>3</cite>.  Activation of different AMPK complexes in skeletal muscle is dependent on exercise intensity and duration. In skeletal muscle, LKB1 is the major upstream kinase responsible for the phosphorylation of α2-containing AMPK complexes in response to high/moderate-intensity and short/limited-duration exercise. In contrast, CaMKKβ phosphorylates and activates α1- containing AMPK complexes during long-term exercise at a low intensity. In human vastus lateralis muscle, AMPK activation is restricted to α2β2γ3 heterotrimers during short (up to 20 min) and intense exercise, whereas the α2β2γ1 and α1β2γ1 complexes appear unchanged or even show decreased activation. When exercise is prolonged, α2β2γ1 heterotrimers are activated. During lower-intensity exercise of longer duration, α2β2γ1 and α1β2γ1  complexes are moderately activated. Thus, in skeletal muscle each AMPK heterotrimer combination is regulated in a distinct manner during contraction depending on exercise intensity and duration, which causes a differential functional response.
 Therefore, AMPK signaling pathway associated with CaMKKβ was excluded from consideration at the first stage of modeling, in accordance with our experimental data.
 ===References===
@@ Line 48: / Line 74: @@
 #2 pmid=20840557	<!-- Laursen 2010 -->
 #3 pmid=29242278	<!-- Kjøbsted 2018 -->
 </biblio>
 [[Category: Human_muscle]]
 [[Category: Signaling Overview]]

@@ Line 31: / Line 31: @@
 Fig. 2. (Laursen 2010)  <cite>2</cite>.  Simplified model of the adenosine monophosphate kinase (AMPK) and calcium–calmodulin kinase (CaMK) signaling pathways, as well as their similar downstream target, the peroxisome proliferator-activated receptor-g coactivator-1a (PGC-1a).
-For moderate and interval high intencity aerobic exercise (50-100% of anaerobic threshold, 60 minutes) the CAMK pathway is not significant pathway. Therefore, only AMPK signaling pathway was used at the first stage of modeling.
+For moderate and high intencity interval aerobic exercise (50-100% of anaerobic threshold, 60 minutes) the CAMK pathway is not significant pathway. Therefore, only AMPK signaling pathway was used at the first stage of modeling.
 The distinct AMPK signaling pathways may be different for various exercise modes.