Makrecka-Kuka 2017 MiP2017

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Marina Makrecka-Kruka
Heart, brain and kidneys: who will survive? Tissue-specific changes in mitochondrial function in the experimental model of endotoxemia.

Link: MiP2017

Makrecka-Kuka M, Korzh S, Vilks K, Dambrova M, Liepinsh E (2017)

Event: MiP2017

COST Action MITOEAGLE

Sepsis, a life-threatening organ dysfunction induced by infection, is a leading cause of death among critically ill patients. Significant impairments in the mitochondrial function are associated with the development of multi-organ failure in sepsis. The aim of the present study was to evaluate the dynamics of heart, brain and kidney mitochondrial function in the experimental model of endotoxemia.

Single injection of LPS (10mg/kg, i.p.) was used to induce endotoxemia in CD1 male mice (n=5 per group). The control animals received saline injection. To exclude fasting effects, during the experiment the animals were deprived of food. Mitochondrial respiration was measured using high-resolution respirometry in permeabilized cardiac fibers and in brain and kidney tissue homogenates 4h- and 24h-post LPS injection. In addition, qRT-PCR analysis was used to measure gene expression.

The gene expression measurements demonstrated that the genes related to inflammation (Il1β, IL6, TNFα, iNOS) are upregulated in all studied tissues, while the genes related to energy metabolism (CPT1A, CPT1B, PDHx) and to mitochondrial function and biogenesis (ATP5O, PGC1a) are downregulated. After 4h of LPS administration, the 2-fold decrease in OXPHOS capacity was observed in kidney homogenate, while the respiration at OXPHOS state in cardiac fibers or brain homogenate was similar to the control group. In the heart 4h-post injection of LPS the significant decrease in mitochondrial fatty acid oxidation was observed. Interestingly, 24h after administration of LPS, the respiration rate in cardiac fibers at OXPHOS state was significantly increased by 20%. The brain mitochondria demonstrated slightly impaired mitochondrial functionality (significant decrease in OXPHOS state respiration by 10%) just 24h after induction of endotoxemia.

In conclusion, the obtained results demonstrate that sepsis-induced mitochondrial damage is tissue specific and time-dependent. The kidney mitochondria are more sensitive to LPS-induced damage compared to brain mitochondria. In the heart, mainly the mitochondrial fatty acid oxidation pathway is impaired. Moreover, during the progression of the disease the maximal phosphorylation is increasing, probably as a mechanism of survival.


Bioblast editor: Kandolf G O2k-Network Lab: LV Riga Makrecka-Kuka M


Labels: Pathology: Sepsis 

Organism: Mouse  Tissue;cell: Heart, Nervous system, Kidney  Preparation: Permeabilized tissue, Homogenate 


Coupling state: OXPHOS 

HRR: Oxygraph-2k 


Affilitations

Makrecka-Kuka M(1), Korzh S(1), Vilks K(1,2), Dambrova M(1), Liepinsh E(1)
  1. Latvian Inst Organic Synthesis
  2. Univ Latvia; Riga, Latvia. - makrecka@farm.osi.lv


Acknowledgments

This study was supported by “Post-doctoral Research Aid” programme project Nr.1.1.1.2/VIAA/1/16/246 and COST Action CA15203 MitoEAGLE.