Kozlov 2010 Abstract IOC60

From Bioblast
Jump to navigation Jump to search
Kozlov AV (2011) Mitochondrial response to shock stimuli in in vitro models. MiPNet15.10.


Kozlov AV, Weidinger A, Muellebner A, Nuernberger S, Kehrer I, Haindl S, Paier-Pourani J, Dungel P, Duvigneau JC, Redl H (2010)

Event: MiPNet15.10_IOC60

It is difficult to clarify mechanisms underlying cellular dysfunction induced by shock in in vivo models, because of their multiple physiological/ pathological regulations. Shock comprises two major pathologic stimuli, namely low levels of oxygen and high levels of inflammatory mediators. In our experiments we used hepatocyte cell line (HEP), liver slices (LS), and liver tissue (LT) to simulate either ischemia or inflammatory response. Confocal and electron microscopy examinations revealed that mitochondria in LS and LT are fragmented while in HEP they built up a network. Hypoxia induced the loss of mitochondrial respiratory activity (in LT & LS), total decrease in ATP levels (LT & LS), the release of ALT/AST, cytoplasmic enzymes, (in LS & HEP), strong degradation of intracellular RNA (in LS & HEP) and an increase in numbers of necrotic, but not apoptotic cells (HC). In LT and LS these changes occurred after 2 h of hypoxia, while HEP required 24 h of ischemia to induce damage to a similar extend. Mitochondrial dysfunction mediated by hypoxia was fully recovered by exogenous cytochrome c (LT). Exposure to naturally generated inflammatory mediators under normoxic conditions resulted in a moderate decrease in ATP levels (LS, LT) and Δψ (HEP), fragmentation of mitochondrial network, and increased levels of mitochondrial ROS (LT & HEP). Experiments with radical scavengers revealed that the major target for mitochondrial ROS are not mitochondria but the expression of specific genes regulating inflammatory and unfolded protein responses. Our data suggest that the lost of cytochrome c and disrupted ATP synthesis are the predominant mitochondrial response to hypoxia but not to inflammatory mediators. The predominant mitochondrial response to inflammatory mediators is increased levels of mitochondrial ROS. Fragmentation of mitochondria is likely of marginal pathological significance in these models.

Keywords: Mitochondria, ROS, Inflammation, Hypoxia

O2k-Network Lab: AT Vienna Kozlov AV

Labels: MiParea: Respiration  Pathology: Sepsis, Other  Stress:Ischemia-reperfusion, Oxidative stress;RONS 

Preparation: Intact organ, Intact cells 

HRR: Oxygraph-2k