lecture 8 adaptions to training part 2

Question 1

how does the muscle adapt in minutes

Answer 1

metabolic and mechanically induced activation of key kinase and phosphatase involved in muscle signal transduction

Question 2

how does the muscle adapt in hours

Answer 2

increased expression of genes encoding mitochondrial and myogenic proteins
increase proliferation and differentiation

Question 3

how does the muscle adapt in days/weeks

Answer 3

increase protein expression and assembly of several multi-subunit respiratory complexes

Question 4

intracelluar signals

Answer 4

Ca2+ activates a variety of signaling
molecules within muscle
– CaMK
– Calcineurin

Question 5

Acute exercise activates signaling
pathways in skeletal muscle

Answer 5

1. intracellular signsls
2. activate signalling pathways
3. increased transcription of target genes
4. increased expression of target proteins

Question 6

CaMK

Answer 6

-Calcium/calmodulin-dependent protein
kinase
* ↑ in intracellular Ca2+ allows CaMK to
become phosphorylated
* p-CaMK is “active” and triggers signaling
pathway leading to gene transcription

Question 7

CaMK signalling

Answer 7

Ca2 activates CaMK that activates transcription which increase expression of mito genes

Question 8

AMP

Answer 8

AMP activates…
à AMP-activated protein kinase (AMPK)
* Phosphorylated AMPK is “active” and
triggers signaling pathway leading to gene
transcription

Question 9

AMPK activity in human skeletal muscle

Answer 9

linear increase from rest to
following exercise of increasing intensity

Question 10

AMPK signaling

Answer 10

AMP activates AMPK that activates transcription which increase expression of mito genes

Question 11

Reactive oxygen species (ROS)

Answer 11

Produced during oxidative phosphorylation
when electron is transferred to molecular
oxygen
* Can be good and bad!
* ROS activate p38 MAPK
* p38 MAPK may also be downstream of
CaMK and AMPK
– Amplify the signals

Question 12

p38 is required for mitochondrial
adaptation to exercise

Answer 12

Muscle-specific
knock-out (MKO) of
p38 MAPK in mice
prevents the increase
in COX IV and
cytochrome c protein
in response to
exercise training

Question 13

p38 MAPK signaling

Answer 13

ROS activates p38 that activates transcription which increase expression of mito genes

ROS, AMPK and CaMK all activate p38 MAPK
– amplification of mitochondrial gene
transcription

Question 14

What is a signaling pathway?

Answer 14

Kinases (e.g., CaMK, AMPK, p38 MAPK)
phosphorylate downstream target proteins
* Adding a phosphate (PO43-) leads to a
conformational change in the target protein,
allowing it to:
a) Interact with other proteins
b) Interact with DNA
c) Catalyze an enzymatic reaction
d) Translocate within the cel

Question 15

Acute exercise activates signalling
pathways in skeletal muscle in detail

Answer 15

1. Ca2+ & AMP & ROS
   2.CaMK & AMPK & p38MAPK 3. mRNA of Mitochondrial gene increases
2. mitochondrial protein content and enzyme activity increase