NUCLEAR REDISTRIBUTION OF EXOGENOUS ADMINISTERED 9- AND 10-HSA, ANALYZED BY MASS SPECTROMETRY

Reactive oxygen species (ROS), at concentrations compatible with those detectable in human pathophysiology, appear able to modulate a number of kinases and phosphatases, redox sensitive transcription factors and genes, and therefore to convey both extracellular and intracellular signals to the nucleus. This type of cell signalling implies the additional involvement of other bioactive molecules that stem from ROS reaction with cell membrane lipids. Studies on lipoperoxidation have substantiated the hypothesis that short-chain peroxidation products, such as 4-hydroxy-2,3-nonenal (4HNE) and malondialdehyde (MDA), long-chain derivatives, such as hydroxystearic acids (HSAs), hydroxyderivatives of arachidonic (HETEs) and linoleic acids (HODEs), as well as hydroxy-derivatives of cholesterol may play important roles in the control of a number of normal and pathological processes [1]. 9- and 10-hydroxy-stearic acids (9-HSA and 10-HSA) are products of endogenous lipoperoxidation identified in several human cell lines: intestinal epithelium (I407), colon adenocarcinoma (HT29), lymphoblastic anemia (Jurkat J6), T lymphocytes, and osteosarcoma (SAOS2, U2OS). The increase of 9-HSA intracellular concentration restores in HT29 the control mechanisms of cell proliferation and differentiation by inhibiting the enzyme histone deacetylase 1 (HDAC1) [2], whereas the effects induced by 10-HSA in the same cell line are still unknown. In the present work we report the concentration-time profile of 9- and 10-HSA in HT29 nuclear fraction after the administration of their deuterated forms (9- and 10-HSA-d), with the aim to active a correlation between the nuclear compartmentation of the hydroxyacids and their biological effects.