Burn Trauma Acutely Increases the Respiratory Capacity and Function of Liver Mitochondria

Fredrick J. Bohanon, Omar Nunez Lopez, David Herndon, Xiaofu Wang, Nisha Bhattarai, Amina El Ayadi, Anesh Prasai, Jayson Jay, Yesenia Rojas-Khalil, Tracy Toliver-Kinsky, Celeste Finnerty, Ravi Radhakrishnan, Craig Porter

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

BACKGROUND:: A complete understanding of the role of the liver in burn-induced hypermetabolism is lacking. We investigated the acute effect of severe burn trauma on liver mitochondrial respiratory capacity and coupling control as well as the signaling events underlying these alterations. METHODS:: Male BALB/c mice (8–12 weeks) received full-thickness scald burns on ∼30% of the body surface. Liver tissue was harvested 24?hours post injury. Mitochondrial respiration was determined by high-resolution respirometry. Citrate synthase activity was determined as a proxy of mitochondrial density. Male Sprague-Dawley rats received full-thickness scald burns to ∼60% of the body surface. Serum was collected 24?hours post injury. HepG2 cells were cultured with serum-enriched media from either sham or burn treated rats. Protein levels were analyzed via western blot. RESULTS:: Mass-specific (p?=?0.01) and mitochondrial-specific (p?=?0.01) respiration coupled to ATP production significantly increased in the liver after burn. The respiratory control ratio for ADP (p?=?0.04) and the mitochondrial flux control ratio (p?=?0.03) were elevated in the liver of burned animals. Complex III and Complex IV protein abundance in the liver increased after burn by 17% and 14%, respectively. Exposure of HepG2 cells to serum from burned rats increased the pAMPKα:AMPKα ratio (p?<?0.001) and levels of SIRT1 (p?=?0.01), Nrf2 (p?<?0.001), and PGC1α (p?=?0.02). CONCLUSIONS:: Severe burn trauma augments respiratory capacity and function of liver mitochondria, adaptations that augment ATP production. This response may be mediated by systemic factors that activate signaling proteins responsible for regulating cellular energy metabolism and mitochondrial biogenesis.

Original languageEnglish (US)
JournalShock
DOIs
StateAccepted/In press - Jul 4 2017

Fingerprint

Liver Mitochondrion
Liver
Wounds and Injuries
Burns
Hep G2 Cells
Respiration
Adenosine Triphosphate
Serum
Citrate (si)-Synthase
Proteins
AMP-Activated Protein Kinases
Electron Transport Complex III
Proxy
Organelle Biogenesis
Adenosine Diphosphate
Energy Metabolism
Sprague Dawley Rats
Western Blotting

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Bohanon, F. J., Lopez, O. N., Herndon, D., Wang, X., Bhattarai, N., Ayadi, A. E., ... Porter, C. (Accepted/In press). Burn Trauma Acutely Increases the Respiratory Capacity and Function of Liver Mitochondria. Shock. https://doi.org/10.1097/SHK.0000000000000935

Burn Trauma Acutely Increases the Respiratory Capacity and Function of Liver Mitochondria. / Bohanon, Fredrick J.; Lopez, Omar Nunez; Herndon, David; Wang, Xiaofu; Bhattarai, Nisha; Ayadi, Amina El; Prasai, Anesh; Jay, Jayson; Rojas-Khalil, Yesenia; Toliver-Kinsky, Tracy; Finnerty, Celeste; Radhakrishnan, Ravi; Porter, Craig.

In: Shock, 04.07.2017.

Research output: Contribution to journalArticle

Bohanon, Fredrick J. ; Lopez, Omar Nunez ; Herndon, David ; Wang, Xiaofu ; Bhattarai, Nisha ; Ayadi, Amina El ; Prasai, Anesh ; Jay, Jayson ; Rojas-Khalil, Yesenia ; Toliver-Kinsky, Tracy ; Finnerty, Celeste ; Radhakrishnan, Ravi ; Porter, Craig. / Burn Trauma Acutely Increases the Respiratory Capacity and Function of Liver Mitochondria. In: Shock. 2017.
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abstract = "BACKGROUND:: A complete understanding of the role of the liver in burn-induced hypermetabolism is lacking. We investigated the acute effect of severe burn trauma on liver mitochondrial respiratory capacity and coupling control as well as the signaling events underlying these alterations. METHODS:: Male BALB/c mice (8–12 weeks) received full-thickness scald burns on ∼30{\%} of the body surface. Liver tissue was harvested 24?hours post injury. Mitochondrial respiration was determined by high-resolution respirometry. Citrate synthase activity was determined as a proxy of mitochondrial density. Male Sprague-Dawley rats received full-thickness scald burns to ∼60{\%} of the body surface. Serum was collected 24?hours post injury. HepG2 cells were cultured with serum-enriched media from either sham or burn treated rats. Protein levels were analyzed via western blot. RESULTS:: Mass-specific (p?=?0.01) and mitochondrial-specific (p?=?0.01) respiration coupled to ATP production significantly increased in the liver after burn. The respiratory control ratio for ADP (p?=?0.04) and the mitochondrial flux control ratio (p?=?0.03) were elevated in the liver of burned animals. Complex III and Complex IV protein abundance in the liver increased after burn by 17{\%} and 14{\%}, respectively. Exposure of HepG2 cells to serum from burned rats increased the pAMPKα:AMPKα ratio (p?<?0.001) and levels of SIRT1 (p?=?0.01), Nrf2 (p?<?0.001), and PGC1α (p?=?0.02). CONCLUSIONS:: Severe burn trauma augments respiratory capacity and function of liver mitochondria, adaptations that augment ATP production. This response may be mediated by systemic factors that activate signaling proteins responsible for regulating cellular energy metabolism and mitochondrial biogenesis.",
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T1 - Burn Trauma Acutely Increases the Respiratory Capacity and Function of Liver Mitochondria

AU - Bohanon, Fredrick J.

AU - Lopez, Omar Nunez

AU - Herndon, David

AU - Wang, Xiaofu

AU - Bhattarai, Nisha

AU - Ayadi, Amina El

AU - Prasai, Anesh

AU - Jay, Jayson

AU - Rojas-Khalil, Yesenia

AU - Toliver-Kinsky, Tracy

AU - Finnerty, Celeste

AU - Radhakrishnan, Ravi

AU - Porter, Craig

PY - 2017/7/4

Y1 - 2017/7/4

N2 - BACKGROUND:: A complete understanding of the role of the liver in burn-induced hypermetabolism is lacking. We investigated the acute effect of severe burn trauma on liver mitochondrial respiratory capacity and coupling control as well as the signaling events underlying these alterations. METHODS:: Male BALB/c mice (8–12 weeks) received full-thickness scald burns on ∼30% of the body surface. Liver tissue was harvested 24?hours post injury. Mitochondrial respiration was determined by high-resolution respirometry. Citrate synthase activity was determined as a proxy of mitochondrial density. Male Sprague-Dawley rats received full-thickness scald burns to ∼60% of the body surface. Serum was collected 24?hours post injury. HepG2 cells were cultured with serum-enriched media from either sham or burn treated rats. Protein levels were analyzed via western blot. RESULTS:: Mass-specific (p?=?0.01) and mitochondrial-specific (p?=?0.01) respiration coupled to ATP production significantly increased in the liver after burn. The respiratory control ratio for ADP (p?=?0.04) and the mitochondrial flux control ratio (p?=?0.03) were elevated in the liver of burned animals. Complex III and Complex IV protein abundance in the liver increased after burn by 17% and 14%, respectively. Exposure of HepG2 cells to serum from burned rats increased the pAMPKα:AMPKα ratio (p?<?0.001) and levels of SIRT1 (p?=?0.01), Nrf2 (p?<?0.001), and PGC1α (p?=?0.02). CONCLUSIONS:: Severe burn trauma augments respiratory capacity and function of liver mitochondria, adaptations that augment ATP production. This response may be mediated by systemic factors that activate signaling proteins responsible for regulating cellular energy metabolism and mitochondrial biogenesis.

AB - BACKGROUND:: A complete understanding of the role of the liver in burn-induced hypermetabolism is lacking. We investigated the acute effect of severe burn trauma on liver mitochondrial respiratory capacity and coupling control as well as the signaling events underlying these alterations. METHODS:: Male BALB/c mice (8–12 weeks) received full-thickness scald burns on ∼30% of the body surface. Liver tissue was harvested 24?hours post injury. Mitochondrial respiration was determined by high-resolution respirometry. Citrate synthase activity was determined as a proxy of mitochondrial density. Male Sprague-Dawley rats received full-thickness scald burns to ∼60% of the body surface. Serum was collected 24?hours post injury. HepG2 cells were cultured with serum-enriched media from either sham or burn treated rats. Protein levels were analyzed via western blot. RESULTS:: Mass-specific (p?=?0.01) and mitochondrial-specific (p?=?0.01) respiration coupled to ATP production significantly increased in the liver after burn. The respiratory control ratio for ADP (p?=?0.04) and the mitochondrial flux control ratio (p?=?0.03) were elevated in the liver of burned animals. Complex III and Complex IV protein abundance in the liver increased after burn by 17% and 14%, respectively. Exposure of HepG2 cells to serum from burned rats increased the pAMPKα:AMPKα ratio (p?<?0.001) and levels of SIRT1 (p?=?0.01), Nrf2 (p?<?0.001), and PGC1α (p?=?0.02). CONCLUSIONS:: Severe burn trauma augments respiratory capacity and function of liver mitochondria, adaptations that augment ATP production. This response may be mediated by systemic factors that activate signaling proteins responsible for regulating cellular energy metabolism and mitochondrial biogenesis.

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