期刊
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
卷 1797, 期 2, 页码 189-196出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbabio.2009.10.001
关键词
Mitochondrial permeability transition; Mitochondria-targeted polyphenol; Reactive oxygen species; Transmembrane potential; Uncoupling
资金
- Italian Foundation for Basic Research (FIRB)
- Italian Association for Cancer Research (AIRC)
- University of Padova
Mitochondria-targeted polyphenols are being developed with the intent to intervene on the levels of reactive oxygen species (ROS) in mitochondria. Polyphenols being more than just anti-oxidants, the interaction of these derivatives with the organelles needs to be characterised. We have studied the effects of two quercetin derivatives, 3-(4-O-triphenylphosphoniumbutyl)quercetin iodide (Q3BTPI) and its tetracetylated analogue (QTA3BTPI), on the inner membrane aspecific permeability, transmembrane voltage difference and respiration of isolated rat liver mitochondria. While the effects of low concentrations were too small to be reliably defined, when used in the 5-20 mu M range these compounds acted as inducers of the mitochondrial permeability transition (MPT), an effect due to pro-oxidant activity. Furthermore, Q3BTPI behaved as an uncoupler of isolated mitochondria, causing depolarisation and stimulating oxygen consumption. When applied to tetramethylrhodamine methyl ester (TMRM)-loaded HepG2 or Jurkat cells uptake of the compounds was predictably associated with a loss of TMRM fluorescence, but there was no indication of MPT induction. A production of superoxide could be detected in some cells upon prolonged incubation of MitoSOX (R)-loaded cells with QTA3BTPI. The overall effects of these model mitochondriotropic polyphenols may thus differ considerably depending on whether their hydroxyls are protected or not and on the experimental system. In vivo assays will be needed for a definitive assessment of their bioactivities. (C) 2009 Elsevier B.V. All rights reserved.
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