Species- and tissue-specific relationships between mitochondrial permeability transition and generation of ROS in brain and liver mitochondria of rats and mice.

Panov A, Dikalov S, Shalbuyeva N, Hemendinger R, Greenamyre JT, Rosenfeld J
Am J Physiol Cell Physiol. 2007 292 (2): C708-18

PMID: 17050617 · DOI:10.1152/ajpcell.00202.2006

In animal models of neurodegenerative diseases pathological changes vary with the type of organ and species of the animals. We studied differences in the mitochondrial permeability transition (mPT) and reactive oxygen species (ROS) generation in the liver (LM) and brain (BM) of Sprague-Dawley rats and C57Bl mice. In the presence of ADP mouse LM and rat LM required three times less Ca(2+) to initiate mPT than the corresponding BM. Mouse LM and BM sequestered 70% and 50% more Ca(2+) phosphate than the rat LM and BM. MBM generated 50% more ROS with glutamate than the RBM, but not with succinate. With the NAD substrates, generation of ROS do not depend on the energy state of the BM. Organization of the respiratory complexes into the respirasome is a possible mechanism to prevent ROS generation in the BM. With BM oxidizing succinate, 80% of ROS generation was energy dependent. Induction of mPT does not affect ROS generation with NAD substrates and inhibit with succinate as a substrate. The relative insensitivity of the liver to systemic insults is associated with its high regenerative capacity. Neuronal cells with low regenerative capacity and a long life span protect themselves by minimizing ROS generation and by the ability to withstand very large Ca(2+) insults. We suggest that additional factors, such as oxidative stress, are required to initiate neurodegeneration. Thus the observed differences in the Ca(2+)-induced mPT and ROS generation may underlie both the organ-specific and species-specific variability in the animal models of neurodegenerative diseases.

MeSH Terms (18)

Animals Brain Calcium Hydrogen Male Membrane Potential, Mitochondrial Mice Mice, Inbred C57BL Mitochondria Mitochondria, Liver Mitochondrial Membranes Organ Specificity Permeability Phosphates Rats Rats, Sprague-Dawley Reactive Oxygen Species Species Specificity

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