turning down the heat: how heat stress affects muscle ... heat stress affects muscle growth and...
TRANSCRIPT
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Turning down the heat: How heat stress affects muscle growth and limits pork production
Joshua Selsby, [email protected] State University
Swine Day
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• Heat stress is the largest impediment to efficient animal agriculture (even in developed countries)• Cost: (lost productivity, mortality, product quality, health care etc.)
• American Agriculture: > $3 billion/year• Global Agriculture: > $100 billion/year
• Heat abatement is the primary strategy to mitigate heat stress • Most developing countries lack the resources to afford this
• Human health concern • Threatens global food security
Heat Stress: Economics and Food Security
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Therapeutic Effects of Hyperthermia
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Pathological heat stress is fundamentally different
Heat StressHeat
StressLess
MuscleLess
Muscle
Intensity? Duration?Mechanism?
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Pathological heat stress is fundamentally different
Heat StressHeat
StressLess
MuscleLess
MuscleSynthesis
Degradation
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Heat StressHeat
StressLess
MuscleLess
Muscle
AA RepartitioningDecreased SynthesisIncreased Degradation
Pathological heat stress is fundamentally different
CalpainsProteasomeOxidative StressAutophagyInflammatory Signaling ER Stress (UPR) ApoptosisMitochondrial dysfunction
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Pig Production
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Pig Production During HS
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Autophagy allows removal of damaged organelles.
2-6 h of HS increases autophagy
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Autophagy allows removal of damaged organelles.
2-6 h of HS increases autophagy
2-6 h of HS increases clearance of damage mitochondria through autophagy
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2-6 hours of Heat StressAfter an initial injury muscle cells respond to heat stress by removing damaged mitochondria or damaged parts of mitochondria via autophagy/mitophagy.
2 4 6
Damaged mitochondria
Autophagy/Mitophagy
Restored/protected mitochondrial pool
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12-24 hours of Heat StressContinued HS causes increased oxidative stress
TN 12 hr HS0.00
0.05
0.10
0.15
0.20
*#
MD
A co
ncen
trat
ion
( M
)
TN 24 hr HS0
1
2
3
4
*
Fold
Cha
nge
12 hrs HS 24 hrs HS
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Autophagy allows removal of damaged organelles.
12 h of HS results:Failure to sustain activationStalling of degradation
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Autophagy allows removal of damaged organelles.
24 h of HS results:Impaired activationBlunted degradationDecreased mitophagy
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24 hours of Heat Stress
Nuclei Lysosomes Autophagosomes
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CYTC COX IV PHB1 SDHA VDAC PDH0
1
2
4
6
TNHSPFTN
* * *
*
*#
##
Rel
ativ
e pr
otei
n ex
pres
sion
Cyto C
Cox IV
VDACPDHSDHA
CIII UQCRC2
CIV MTCO1
CII SDHB
0
1
2
3 TN24 h HS* *
* ** *
Rela
tive
Prot
ein
Abun
danc
e
Continued HS causes an accumulation of mitochondriaNote: these are likely damaged, pro-oxidant mitochodnria
12-24 hours of Heat Stress
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Chronology of Heat StressAfter an initial injury muscle cells respond to heat stress by removing damaged mitochondria or damaged parts of mitochondria via autophagy/mitophagy.
2 6 12 24
Effective response Collapse of response with continued heat stress
Over time this process appears to fail allowing the accumulation of oxidativelymodified proteins and damaged mitochondria.
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/AO
Proposed Mechanism
CHOLipidAA
ATP
X
ROS
Apoptosis
Ca2+
Cytosolic ROS
Autophagy
X?
?
?
?
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• Complete a chronology of heat stress-mediated changes in skeletal muscle.
• Determine the extent to which cytosolic sources of free radical production contribute to impaired efficiency.
• Determine the extent to which:Mito-protection…Stimulation of autophagy…
…attenuate losses in efficiency
Future Research Objectives
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Acknowledgements
Contributions by
• Shanthi Ganesan• Alex Brownstein
• Baumgard Lab• Gabler Lab• Rhoads Lab
Supported by
• USDA/NIFA Grant No. 2011-67003-30007
• USDA/NIFA Grant No. 2014-67015-21627
• Wise Burroughs Endowment
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Questions