Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2006

Open Access 01-12-2006 | Research article

Changes in liver mitochondrial plasticity induced by brain tumor

Authors: Daniel Pouliquen, Christophe Olivier, Emilie Debien, Khaled Meflah, François M Vallette, Jean Menanteau

Published in: BMC Cancer | Issue 1/2006

Login to get access

Abstract

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.

Conclusion

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.
Appendix
Available only for authorised users
Literature
1.
Diamandis EP: Mass spectrometry as a diagnostic and a cancer biomarker discovery tool. Mol Cell Proteomics. 2004, 3.4: 367-378. 10.1074/mcp.R400007-MCP200.CrossRef
2.
Deans C, Wigmore SJ: Systemic inflammation, cachexia and prognosis in patients with cancer. Curr Opin Clin Nutr Metab Care. 2005, 8: 265-269.CrossRefPubMed
3.
Tisdale MJ: Metabolic abnormalities in cachexia and anorexia. Nutrition. 2000, 16: 1013-1014. 10.1016/S0899-9007(00)00409-3.CrossRefPubMed
4.
Pouliquen D, Foussard F, Tanguy G, Roux J, Malthièry Y: Total and structured water in cancer: an NMR experimental study of serum and tissues in DMBA-induced OF1 mice. Cell Mol Biol. 2001, 47: 947-957.PubMed
5.
Jendrasiak GL: The hydration of phospholipids and its biological significance. J Nutr Biochem. 1996, 7: 599-609. 10.1016/S0955-2863(96)00118-0.CrossRef
6.
Fernandez-Checa JC, Kaplowitz N: Hepatic mitochondrial glutathione: transport and role in disease and toxicity. Toxicol Appl Pharmacol. 2005, 204: 263-273. 10.1016/j.taap.2004.10.001.CrossRefPubMed
7.
Pouliquen D, Bellot G, Guihard G, Fichet P, Meflah K, Vallette FM: Mitochondrial membrane permeabilization produced by PTP, Bax and apoptosis: a 1H-NMR relaxation study. Cell Death Differ. 2006, 13: 301-310. 10.1038/sj.cdd.4401731.CrossRefPubMed
8.
Colell A, Garcia-Ruiz C, Lluis JM, Coll O, Mari M, Fernandez-Checa JC: Cholesterol impairs the adenine nucleotide translocator-mediated mitochondrial permeability transition through altered membrane fluidity. J Biol Chem. 2003, 278: 33928-33935. 10.1074/jbc.M210943200.CrossRefPubMed
9.
Mourad PD, Farrell L, Stamps LD, Chicoine DL, Silbergeld DL: Why are systemic glioblastoma metastases rare ? Systemic and cerebral growth of mouse glioblastoma. Surg Neurol. 2005, 63: 511-519. 10.1016/j.surneu.2004.08.062.CrossRefPubMed
10.
Hortelano S, Garcia-Martin ML, Cerdan S, Castrillo A, Alvarez AM, Bosca L: Intracellular water motion decreases in apoptotic macrophages after caspase activation. Cell Death Differ. 2001, 8: 1022-1028. 10.1038/sj.cdd.4400913.CrossRefPubMed
11.
Rickwood D, Wilson MT, Darley-Usmar VM: Isolation and characteristics of intact mitochondria. Mitochondria, a practical approach. Edited by: Darley-Usmar VM, Rickwood D, Wilson MT. 1987, Oxford, IRL Press, 1-16.
12.
Koestner A, Swenberg JA, Wechsler W: Transplacental production with ethylnitrosourea of neoplasms of the nervous system in Sprague-Dawley rats. Am J Pathol. 1971, 63: 37-56.PubMedPubMedCentral
13.
Gallier J, Rivet P, de Certaines JD: 1H- and 2H-NMR study of bovine seram albumin solutions. Biochim Biophys Acta. 1987, 915: 1-18.CrossRefPubMed
14.
Bligh EG, Dyer WJ: A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959, 37: 911-917.CrossRefPubMed
15.
Zlatkis A, Zak B: Study of a new cholesterol reagent. Anal Biochem. 1969, 29: 143-148. 10.1016/0003-2697(69)90017-7.CrossRefPubMed
16.
Juin P, Pelletier M, Oliver L, Tremblais K, Grégoire M, Meflah K, Vallette FM: Induction of a caspase-3-like activity by calcium in normal cytosolic extracts triggers nuclear apoptosis in a cell-free system. J Biol Chem. 1998, 273: 17559-17564. 10.1074/jbc.273.28.17559.CrossRefPubMed
17.
Mentré P: An introduction to « water in the cell »: tamed hydra ?. Cell Mol Biol. 2001, 47: 709-715.PubMed
18.
Kouda K, Nakamura H, Kohno H, Ha-Kawa SK, Tokunaga R, Sawada S: Dietary restriction: effects of short-term fasting on protein uptake and cell death/proliferation in the rat liver. Mech Ageing Dev. 2004, 125: 375-380. 10.1016/j.mad.2004.02.006.CrossRefPubMed
19.
Mclntyre GI: Cell hydration as the primary factor in carcinogenesis: a unifying concept. Med Hypoth. 2006, 66: 518-526. 10.1016/j.mehy.2005.09.022.CrossRef
20.
21.
Simon SA, McIntosh TJ, Latorre R: Influence of cholesterol on water penetration into bilayers. Science. 1982, 216: 65-67. 10.1126/science.7063872.CrossRefPubMed
22.
Campbell AM, Capuano A, Chan SH: A cholesterol-binding and transporting protein from rat liver mitochondria. Biochim Biophys Acta. 2002, 1567: 123-132. 10.1016/S0005-2736(02)00607-7.CrossRefPubMed
23.
O'Rourke B: Pathophysiological and protective roles of mitochondrial ion channels. J Physiol. 2000, 529.1: 23-36. 10.1111/j.1469-7793.2000.00023.x.CrossRef
24.
Brookes PS: Mitochondrial nitric oxide synthase. Mitochondrion. 2004, 3: 187-204. 10.1016/j.mito.2003.10.001.CrossRefPubMed
25.
Chakravarty PK, Ghosh A, Chowdhury JR: Plasma and erythrocyte copper level as an indicator of disease activity during malignancy. Canc Lett. 1994, 84: 177-182. 10.1016/0304-3835(94)90373-5.CrossRef
26.
Ettinger MJ: Hepatic copper metabolism. Hepatology, a textbook of liver disease. Edited by: Zakim D, Boyer TD. 1996, Philadelphia, W. B. Saunders Company, 1: 554-563. 3
27.
Khalimonchuk O, Rödel G: Biogenesis of cytochrome c oxidase. Mitochondrion. 2005, 5: 363-388. 10.1016/j.mito.2005.08.002.CrossRefPubMed
28.
Frey HE, Knispel RR, Kruuv J, Sharp AR, Thompson RT, Pintar MM: Proton spin-lattice relaxation studies of nonmalignant tissues of tumorous mice. J Natl Canc Inst. 1972, 49: 903-906.
29.
Hollis DP, Saryan LA, Economou JS, Eggleston JC, Czeisler JL, Morris HP: Nuclear magnetic resonance studies of cancer. V. Appearance and development of a tumor systemic effect in serum and tissues. J Natl Canc Inst. 1974, 53: 807-815.
30.
Negendank W, Corbett T, Crowley M, Kellogg C: Evidence for a contribution of paramagnetic ions to water proton spin-lattice relaxation in normal and malignant mouse tissues. Magn Reson Med. 1991, 18: 280-293.CrossRefPubMed
31.
Gawrisch K, Ruston D, Zimmerberg J, Parsegian VA, Rand RP, Fuller N: Membrane dipole potentials, hydration forces, and the ordering of water at membrane surfaces. Biophys J. 1992, 61: 1213-1223.CrossRefPubMedPubMedCentral
32.
Wiggins PM, Van Ryn RT: Changes in ionic selectivity with changes in density in gels and cells. Biophys J. 1987, 58: 585-596.CrossRef
33.
Herrera B, Fernandez M, Alvarez AM, Roncero C, Benito M, Gil J, Fabregat I: Activation of caspases occurs downstream from radical oxygen species production, Bcl-xL down-regulation, and early cytochrome c release in apoptosis induced by transforming growth β factor in rat fetal hepatocytes. Hepatology. 2001, 34: 548-556. 10.1053/jhep.2001.27447.CrossRefPubMed
Metadata
Title
Changes in liver mitochondrial plasticity induced by brain tumor
Authors
Daniel Pouliquen
Christophe Olivier
Emilie Debien
Khaled Meflah
François M Vallette
Jean Menanteau
Publication date
01-12-2006
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2006
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-6-234

Other articles of this Issue 1/2006

BMC Cancer 1/2006 Go to the issue

Research article

AIB1 gene amplification and the instability of polyQ encoding sequence in breast cancer cell lines

Research article

TSPY potentiates cell proliferation and tumorigenesis by promoting cell cycle progression in HeLa and NIH3T3 cells

Research article

Signs of positive selection of somatic mutations in human cancers detected by EST sequence analysis

Research article

Microarray-based identification and RT-PCR test screening for epithelial-specific mRNAs in peripheral blood of patients with colon cancer

Case report

Hidden chromosomal abnormalities in pleuropulmonary blastomas identified by multiplex FISH

Research article

Gene expression patterns associated with p53 status in breast cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits