| 1. |
- Pagano, G., et al.
(author)
-
Fanconi anaemia proteins : Major roles in cell protection against oxidative damage
- 2003
-
In: Bioessays. - : Wiley. - 0265-9247 .- 1521-1878. ; 25:6, s. 589-595
-
Research review (peer-reviewed)abstract
- Fanconi anaemia (FA) is a cancer-prone genetic disorder that is characterised by cytogenetic instability and redox abnormalities. Although rare subtypes of FA (B, D1 and D2) have been implicated in DNA repair through links with BRCA1 and BRCA2, such a role has yet to be demonstrated for gene products of the common subtypes. Instead, these products have been strongly implicated in xenobiotic metabolism and redox homeostasis through interactions of FANCC with cytochrome P-450 reductase and with glutathione S-transferase, and of FANCG with cytochrome P-450 2E1, as well as redox-dependent signalling through an interaction between FANCA and Akt kinase. We hypothesise that FA proteins act directly (via FANCC and FANCG) and indirectly (via FANCA, BRCA2 and FANCD2) with the machinery of cellular defence to modulate oxidative stress. The latter interactions may co-ordinate the link between the response to DNA damage and oxidative stress parameters (3, 6-12). © 2003 Wiley Periodicals, Inc.
|
|
| 2. |
- Gauden, Magdalena, et al.
(author)
-
Role of Solvent, pH, and Molecular Size in Excited-State Deactivation of Key Eumelanin Building Blocks: Implications for Melanin Pigment Photostability.
- 2008
-
In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 130:50, s. 17038-17043
-
Journal article (peer-reviewed)abstract
- Ultrafast time-resolved fluorescence spectroscopy has been used to investigate the excited-state dynamics of the basic eumelanin building block 5,6-dihydroxyindole-2-carboxylic acid (DHICA), its acetylated, methylated, and carboxylic ester derivatives, and two oligomers, a dimer and a trimer in the O-acetylated forms. The results show that (1) excited-state decays are faster for the trimer relative to the monomer; (2) for parent DHICA, excited-state lifetimes are much shorter in aqueous acidic medium (380 ps) as compared to organic solvent (acetonitrile, 2.6 ns); and (3) variation of fluorescence spectra and excited-state dynamics can be understood as a result of excited-state intramolecular proton transfer (ESIPT). The dependence on the DHICA oligomer size of the excited-state deactivation and its ESIPT mechanism provides important insight into the photostability and the photoprotective function of eumelanin. Mechanistic analogies with the corresponding processes in DNA and other biomolecules are recognized.
|
|
| 3. |
- Huijser, Annemarie, et al.
(author)
-
UV-Dissipation Mechanisms in the Eumelanin Building Block DHICA
- 2010
-
In: ChemPhysChem. - : Wiley. - 1439-7641 .- 1439-4235. ; 11:11, s. 2424-2431
-
Journal article (peer-reviewed)abstract
- The UV-dissipative mechanisms of the eumelanin building block 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and the 4,7-dideutero derivative (DHICA-d(2)) in buffered H2O or D2O have been characterized by using ultrafast time-resolved fluorescence spectroscopy. Excitation of the carboxylate anion form, the dominating state at neutral pH, leads to dual fluorescence. The band peaking at lambda = 378 nm is caused by emission from the excited initial geometry. The second band around lambda = 450 nm is owed to a complex formed between the monoanion and specific buffer components. In the absence of complex formation, the mono-anion solely decays non-radiatively or by emission with a lifetime of about 2.1 ns. Excitation of the neutral carboxylic acid state, which dominates at acidic pH, leads to a weak emission around lambda = 427 nm with a short lifetime of 240 ps. This emission originates from the zwitterionic state, formed upon excitation of the neutral state by sub-ps excited-state intramolecular proton transfer (ESIPT) between the carboxylic acid group and the indole nitrogen. Future studies will unravel whether this also occurs in larger building blocks and ESIPT is a built-in photoprotective mechanism in epidermal eumelanin.
|
|
| 4. |
|
|
