Changes in liver mitochondrial plasticity induced by brain tumor.
BACKGROUND
Accumulating data suggest that liver is a major target organ of systemic effects observed in the presence of a cancer. In this study, we investigated the consequences of the presence of chemically induced brain tumors in rats on biophysical parameters accounting for the dynamics of water in liver mitochondria.


METHODS
Tumors of the central nervous system were induced by intraveinous administration of ethylnitrosourea (ENU) to pregnant females on the 19th day of gestation. The mitochondrial crude fraction was isolated from the liver of each animal and the dynamic parameters of total water and its macromolecule-associated fraction (structured water, H2Ost) were calculated from Nuclear Magnetic Resonance (NMR) measurements.


RESULTS
The presence of a malignant brain tumor induced a loss of water structural order that implicated changes in the physical properties of the hydration shells of liver mitochondria macromolecules. This feature was linked to an increase in the membrane cholesterol content, a way to limit water penetration into the bilayer and then to reduce membrane permeability. As expected, these alterations in mitochondrial plasticity affected ionic exchanges and led to abnormal features of mitochondrial biogenesis and caspase activation.


CONCLUSIONS
This study enlightens the sensitivity of the structured water phase in the liver mitochondria machinery to external conditions such as tumor development at a distant site. The profound metabolic and functional changes led to abnormal features of ion transport, mitochondrial biogenesis and caspase activation.
Pouliquen
Daniel
D
Inserm, U601, Equipe Apoptose et progression tumorale, F-44000, Nantes, France. daniel.pouliquen@univ-nantes.fr
Olivier
Christophe
C
Debien
Emilie
E
Meflah
Khaled
K
Vallette
François M
FM
Menanteau
Jean
J
D000818:Animals; D001932:Brain Neoplasms / Q000737:chemistry* / Q000201:enzymology; D020169:Caspases / Q000378:metabolism; D002784:Cholesterol / Q000032:analysis; D005231:Fatty Acids, Unsaturated / Q000032:analysis; D005260:Female; D007477:Ions / Q000032:analysis; D008099:Liver / Q000201:enzymology; D008930:Mitochondria, Liver / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D051381:Rats; D014867:Water / Q000737:chemistry*
D005231:Fatty Acids, Unsaturated; D007477:Ions; D014867:Water; D002784:Cholesterol; D020169:Caspases