SummaryThe unequivocal demonstration that the carbonate radical (CO 3 .7 ) is produced from the reaction between the ubiquitous carbon dioxide and peroxynitrite, renewed the interest in the pathogenic roles of oxidants derived from the main physiological buffer, the bicarbonate-carbon dioxide pair. Here, we review the biochemical properties of both the carbonate radical and peroxymonocarbonate (HCO 4 7 ), and discuss the evidence of their formation under physiological conditions. Overall, the review emphasizes the recognition of the biological relevance of oxidants derived from the main physiological buffer as a crucial step into the understanding and control of numerous pathological states. IUBMB Life, 59: 255-262, 2007

No abstract

We characterized the pro-apoptotic activity of two new synthesized isatin-Schiff base copper(II) complexes, obtained from isatin and 1,3-diaminopropane or 2-(2-aminoethyl)pyridine: (Cu(isapn)) and (Cu(isaepy) 2 ), respectively. We demonstrated that these compounds trigger apoptosis via the mitochondrial pathway. The early induction of the p53/p21 system indicates a role for p53 in cell death, however, experiments carried out with small interfering RNA against p53, or with cells lacking p53, support that a p53-independent mechanism can also occur. The extent of apoptosis mirrors the kinetics of intracellular copper uptake. Particularly, Cu(isaepy) 2 enters the cells more efficiently and specifically damages nuclei and mitochondria, as evidenced by atomic absorption analysis of copper content and by the extent of nuclear and mitochondrial integrity. Conversely, Cu(isapn), although less permeable, induces a widespread oxidative stress, as demonstrated by analyses of reactive oxygen species concentration, and oxidation of proteins and lipids. The increase of the antioxidant defense, through the overexpression of Cu,Zn-SOD, partially counteracts cell death; whereas retinoic acid-mediated differentiation completely rescues cells from apoptosis induced by both compounds. The activation of JNK-and Akt-mediated phosphorylative pathways has been found to be not functional for apoptosis induction. On the contrary, apoptosis significantly decreased when the analogous zinc complex was used or when Cu(isaepy) 2 was incubated in the presence of a copper chelator. Altogether, our data provide evidence for a dual role of these copper(II) complexes: they are able to vehicle copper into the cell, thus producing reactive oxygen species, and could behave as delocalized lipophilic cation-like molecules, thus specifically targeting organelles.

No abstract

Peroxymonocarbonate (HCO4-) is an oxidant whose existence in equilibrium with hydrogen peroxide and bicarbonate has been known since the 1980s. More recently, peroxymonocarbonate has been proposed to mediate oxidative processes stimulated by the bicarbonate/carbon dioxide pair. To better understand this emerging biological oxidant, we re-examined the kinetics of its formation from hydrogen peroxide and bicarbonate/carbon dioxide by 13C NMR. Also, we studied its role in the accelerating effects of bicarbonate on biothiol (GSH and BSA-cysSH) peroxidation by kinetics and product analysis. The rate constants for peroxymonocarbonate formation and decay were estimated and Keq values determined (pH 7.2, at 25 and 37 degrees C; in the absence and presence of BSA and liposomes of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine phosphatidylcholine). Noteworthy is the fact the rate constant for peroxymonocarbonate formation estimated here (k1 approximately 10-2 M-1 s-1) was more than 1 order of magnitude higher than a previously reported value. Also, peroxymonocarbonate equilibrium was shown to be affected by BSA, liposomes, and a carbonic anhydrase mimetic. The Keq values determined in the absence and presence of BSA (0.35 and 0.48 M-1, respectively, at 37 degrees C) were employed to analyze the kinetics of BSA-cysSH and GSH peroxidation in the presence of bicarbonate (2-25 mM). A good fit of experimental data with simulations indicated that peroxymonocarbonate is the main species responsible for biothiol peroxidation in the presence of bicarbonate. The results indicate that peroxymonocarbonate is a feasible biological oxidant, in addition to supporting emerging data that the main physiological buffer is redox active.