Mitochondrial dysfunction in rat splenocytes following hemorrhagic shock

Marie Warren, Kumar Subramani, Richard Schwartz, Raghavan Raju

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The regulation of mitochondrial function is critical in cellular homeostasis following hemorrhagic shock. Hemorrhagic shock results in fluid loss and reduced availability of oxygen and nutrients to tissues. The spleen is a secondary lymphoid organ playing a key role in ‘filtering the blood’ and in the innate and adaptive immune responses. To understand the molecular basis of hemorrhagic shock, we investigated the changes in splenocyte mitochondrial respiration, and concomitant immune and metabolic alterations. The hemorrhagic injury (HI) in our rat model was induced by bleeding 60% of the total blood volume followed by resuscitation with Ringers lactate. Another group of animals was subjected to hemorrhage, but did not receive fluid resuscitation. Oxygen consumption rate of splenocytes were determined using a Seahorse analyzer. We found a significantly reduced oxygen consumption rate in splenocytes following HI compared to sham operated rats. The mitochondrial stress test revealed a decreased basal oxygen consumption rate, ATP production, maximal respiration and spare respiratory capacity. The mitochondrial membrane potential, and citrate synthase activity, were also reduced in the splenocytes following HI. Hypoxic response in the splenocyte was confirmed by increased gene expression of Hif1α. Elevated level of mitochondrial stress protein, hsp60 and induction of high mobility group box1 protein (HMGB1) were observed in splenocytes following HI. An increased inflammatory response was demonstrated by significantly increased expression of IL-6, IFN-β, Mip-1α, IL-10 and NFκbp65. In summary, we conclude that splenocyte oxidative phosphorylation and metabolism were severely compromised following HI.

Original languageEnglish (US)
Pages (from-to)2526-2533
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1863
Issue number10
DOIs
StatePublished - Oct 2017

Fingerprint

Hemorrhagic Shock
Oxygen Consumption
Wounds and Injuries
Resuscitation
Respiration
High Mobility Group Proteins
Hemorrhage
Smegmamorpha
Citrate (si)-Synthase
Mitochondrial Membrane Potential
Mitochondrial Proteins
Oxidative Phosphorylation
Adaptive Immunity
Heat-Shock Proteins
Blood Volume
Exercise Test
Innate Immunity
Interleukin-10
Interleukin-6
Homeostasis

Keywords

  • Hemorrhage
  • Mitochondrial function
  • Shock
  • Trauma

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

Cite this

Mitochondrial dysfunction in rat splenocytes following hemorrhagic shock. / Warren, Marie; Subramani, Kumar; Schwartz, Richard; Raju, Raghavan.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1863, No. 10, 10.2017, p. 2526-2533.

Research output: Contribution to journalArticle

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