Effect of estrogen on mitochondrial function and intracellular stress markers in rat liver and kidney following trauma-hemorrhagic shock and prolonged hypotension

Andrey V. Kozlov, J. Catharina Duvigneau, Tanya C. Hyatt, Raghavan Pillai Raju, Tricia Behling, Romana T. Hartl, Katrin Staniek, Ingrid Miller, Wolfgang Gregor, Heinz Redl, Irshad H. Chaudry

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Trauma-hemorrhage (T-H) is known to impair tissue perfusion, leading to tissue hypoxia, and thus affecting mitochondria, the organelles with the highest oxygen demand. In a model of T-H and prolonged hypotension without fluid resuscitation, administration of a small volume of 17β-estradiol (E2), but not vehicle, prolonged the survival of rats for 3 h, even in the absence of fluid resuscitation. The main finding of this study is that T-H followed by prolonged hypotension significantly affects mitochondrial function, endoplasmic reticulum (ER) stress markers and free iron levels, and that E2 ameliorated all these changes. All of these changes were observed in the liver but not in the kidney. The sensitivity of mitochondrial respiration to exogenous cytochrome c can reflect increased permeability of the outer mitochondrial membrane for cytochrome c. Increased levels of free iron are indicative of oxidative stress, but neither oxidative nor nitrosylative stress markers changed. The spliced isoform of XBP1 mRNA (an early marker of ER stress) and the expression of C/EBP homologous protein (CHOP) (a protein regulating ER stress-induced apoptosis) were elevated in T-H animals but remained unchanged if T-H rats received E2. Both the prevention of elevated sensitivity of mitochondrial respiration to cytochrome c and a decrease in ER stress by E2 maintain functional integrity of the liver and may help the organ during prolonged hypotension and following resuscitation. A decrease in free iron levels by E2 is more relevant for resuscitation, often accompanied by oxidative stress reaction. Thus, E2 appears to be a novel hormonal adjunct that prolongs permissive hypotension during lengthy transportation of the injured patient between the injury site and the hospital in both civilian and military injuries.

Original languageEnglish (US)
Pages (from-to)254-261
Number of pages8
JournalMolecular Medicine
Volume16
Issue number7-8
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

Fingerprint

Hemorrhagic Shock
Hypotension
Estrogens
Endoplasmic Reticulum Stress
Kidney
Liver
Resuscitation
Wounds and Injuries
Hemorrhage
Cytochromes c
Iron
Respiration
Oxidative Stress
Transportation of Patients
Transcription Factor CHOP
Cytochromes a
RNA Isoforms
Mitochondrial Membranes
Organelles
Estradiol

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)
  • Medicine(all)

Cite this

Effect of estrogen on mitochondrial function and intracellular stress markers in rat liver and kidney following trauma-hemorrhagic shock and prolonged hypotension. / Kozlov, Andrey V.; Catharina Duvigneau, J.; Hyatt, Tanya C.; Raju, Raghavan Pillai; Behling, Tricia; Hartl, Romana T.; Staniek, Katrin; Miller, Ingrid; Gregor, Wolfgang; Redl, Heinz; Chaudry, Irshad H.

In: Molecular Medicine, Vol. 16, No. 7-8, 01.01.2010, p. 254-261.

Research output: Contribution to journalArticle

Kozlov, AV, Catharina Duvigneau, J, Hyatt, TC, Raju, RP, Behling, T, Hartl, RT, Staniek, K, Miller, I, Gregor, W, Redl, H & Chaudry, IH 2010, 'Effect of estrogen on mitochondrial function and intracellular stress markers in rat liver and kidney following trauma-hemorrhagic shock and prolonged hypotension', Molecular Medicine, vol. 16, no. 7-8, pp. 254-261. https://doi.org/10.2119/molmed.2009.00184
Kozlov, Andrey V. ; Catharina Duvigneau, J. ; Hyatt, Tanya C. ; Raju, Raghavan Pillai ; Behling, Tricia ; Hartl, Romana T. ; Staniek, Katrin ; Miller, Ingrid ; Gregor, Wolfgang ; Redl, Heinz ; Chaudry, Irshad H. / Effect of estrogen on mitochondrial function and intracellular stress markers in rat liver and kidney following trauma-hemorrhagic shock and prolonged hypotension. In: Molecular Medicine. 2010 ; Vol. 16, No. 7-8. pp. 254-261.
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AU - Raju, Raghavan Pillai

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AU - Hartl, Romana T.

AU - Staniek, Katrin

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AU - Gregor, Wolfgang

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AU - Chaudry, Irshad H.

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