Advanced

Diverse and Tissue Specific Mitochondrial Respiratory Response in A Mouse Model of Sepsis-Induced Multiple Organ Failure.

Karlsson, Michael LU ; Hara, Naomi LU ; Morata, Saori; Sjövall, Fredrik LU ; Kilbaugh, Todd; Hansson, Magnus LU ; Uchino, Hiroyoki and Elmer, Eskil LU (2016) In Shock 45(4). p.404-410
Abstract
Mitochondrial function is thought to play a role in sepsis-induced multiple organ failure. However, the temporal and organ specific alterations in mitochondrial function has yet to be fully elucidated. Many studies show reduced phosphorylating capacity while others have indicated that mitochondrial respiration is enhanced. The objective of the study was to evaluate the temporal dynamics of brain and liver mitochondrial function in a mouse model of sepsis.Sepsis was induced by cecal ligation and puncture. Controls were sham operated. Using high-resolution respirometry, brain and liver homogenates from 31 C57BL/6 mice were analyzed at either 6 hours or 24 hours. ROS-production was simultaneously measured in brain samples using... (More)
Mitochondrial function is thought to play a role in sepsis-induced multiple organ failure. However, the temporal and organ specific alterations in mitochondrial function has yet to be fully elucidated. Many studies show reduced phosphorylating capacity while others have indicated that mitochondrial respiration is enhanced. The objective of the study was to evaluate the temporal dynamics of brain and liver mitochondrial function in a mouse model of sepsis.Sepsis was induced by cecal ligation and puncture. Controls were sham operated. Using high-resolution respirometry, brain and liver homogenates from 31 C57BL/6 mice were analyzed at either 6 hours or 24 hours. ROS-production was simultaneously measured in brain samples using fluorometry.Septic brain tissue exhibited an early increased uncoupling of respiration. Temporal changes between the two time points were diminutive and no difference in ROS-production was detected.Liver homogenate from the septic mice displayed a significant increase of the respiratory control ratio at 6 hours. In the 24-hour group, the rate of maximal oxidative phosphorylation, as well as LEAK respiration, was significantly increased compared to controls and the resultant respiratory control ratio was also significantly increased. Maximal Protonophore-induced respiratory (uncoupled) capacity was similar between the two treatment groups.The present study suggests a diverse and tissue specific mitochondrial respiratory response to sepsis. The brain displayed an early impaired mitochondrial respiratory efficiency. In the liver the primary finding was a substantial activation of the maximal phosphorylating capacity. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Shock
volume
45
issue
4
pages
404 - 410
publisher
BioMedical Press
external identifiers
  • pmid:26536202
  • scopus:84946434064
  • wos:000374760700009
ISSN
1540-0514
DOI
10.1097/SHK.0000000000000525
language
English
LU publication?
yes
id
72e25f2f-bd0a-4544-abd0-0a000ea49576 (old id 8243151)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26536202?dopt=Abstract
date added to LUP
2015-12-02 22:32:38
date last changed
2017-11-19 04:18:28
@article{72e25f2f-bd0a-4544-abd0-0a000ea49576,
  abstract     = {Mitochondrial function is thought to play a role in sepsis-induced multiple organ failure. However, the temporal and organ specific alterations in mitochondrial function has yet to be fully elucidated. Many studies show reduced phosphorylating capacity while others have indicated that mitochondrial respiration is enhanced. The objective of the study was to evaluate the temporal dynamics of brain and liver mitochondrial function in a mouse model of sepsis.Sepsis was induced by cecal ligation and puncture. Controls were sham operated. Using high-resolution respirometry, brain and liver homogenates from 31 C57BL/6 mice were analyzed at either 6 hours or 24 hours. ROS-production was simultaneously measured in brain samples using fluorometry.Septic brain tissue exhibited an early increased uncoupling of respiration. Temporal changes between the two time points were diminutive and no difference in ROS-production was detected.Liver homogenate from the septic mice displayed a significant increase of the respiratory control ratio at 6 hours. In the 24-hour group, the rate of maximal oxidative phosphorylation, as well as LEAK respiration, was significantly increased compared to controls and the resultant respiratory control ratio was also significantly increased. Maximal Protonophore-induced respiratory (uncoupled) capacity was similar between the two treatment groups.The present study suggests a diverse and tissue specific mitochondrial respiratory response to sepsis. The brain displayed an early impaired mitochondrial respiratory efficiency. In the liver the primary finding was a substantial activation of the maximal phosphorylating capacity.},
  author       = {Karlsson, Michael and Hara, Naomi and Morata, Saori and Sjövall, Fredrik and Kilbaugh, Todd and Hansson, Magnus and Uchino, Hiroyoki and Elmer, Eskil},
  issn         = {1540-0514},
  language     = {eng},
  number       = {4},
  pages        = {404--410},
  publisher    = {BioMedical Press},
  series       = {Shock},
  title        = {Diverse and Tissue Specific Mitochondrial Respiratory Response in A Mouse Model of Sepsis-Induced Multiple Organ Failure.},
  url          = {http://dx.doi.org/10.1097/SHK.0000000000000525},
  volume       = {45},
  year         = {2016},
}