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Fatty acids and other components of the diet may modulate, among others, mechanisms involved in homeostasis, aging, and age-related diseases. Using a proteomic approach, we have studied how dietary oil affected plasma proteins in young (6 months) or old (24 months) rats fed lifelong with two experimental diets enriched in either sunflower or virgin olive oil. After the depletion of the most abundant proteins, levels of less abundant proteins were studied using two-dimensional electrophoresis and mass spectrometry. Our results showed that compared with the sunflower oil diet, the virgin olive oil diet induced significant decreases of plasma levels of acute phase proteins such as inter-alpha inhibitor H4P heavy chain (at 6 months), hemopexin precursor (at 6 and 24 months), preprohaptoglobin precursor (at 6 and 24 months), and α-2-HS glycoprotein (at 6 and 24 months); antioxidant proteins such as type II peroxiredoxin (at 24 months); proteins related with coagulation such as fibrinogen γ-chain precursor (at 24 months), T-kininogen 1 precursor (at 6 and 24 months), and apolipoprotein H (at 6 and 24 months); or with lipid metabolism and transport such as apolipoprotein E (at 6 and 24 months) and apolipoprotein A-IV (at 24 months). The same diet increased the levels of apolipoprotein A-1 (at 6 and 24 months), diminishing in general the changes that occurred with age. Our unbiased analysis reinforces the beneficial role of a diet rich in virgin olive oil compared with a diet rich in sunflower oil, modulating inflammation, homeostasis, oxidative stress, and cardiovascular risk during aging. Show less

Through microarray analyses, we identified the Mpped2 gene as differentially expressed in two neuroblastoma cell lines induced to differentiation with all-trans retinoic acid. Mpped2 codes for a new metallophosphodiesterase protein, the expression of which inhibits cell proliferation and soft agar colony formation in SH -SY5Y cells. This inhibition is concomitant to an increased proportion of the cells in G0/G1 phase and enhanced caspase 3 activation, effects not seen for the other phosphodiesterases. A Mpped2-null mutation (H67R) abrogates these functions, which indicates that the biochemical activity of Mpped2 is advantageous for cancer suppression. Expression analyses in the "Los Angeles" and "Essen" neuroblastoma gene-array data sets show that increased expression of Mpped2 is associated with good patient prognosis according to Kaplan-Meier analyses. Tumorigenic assays in mice show that overexpression of Mpped2 improves survival rate, substantially impairs tumor growth and induces neuronal differentiation. Altogether, these data show that Mpped2 expression impairs neuroblastoma tumorigenesis, and they establish a basis for future therapeutic applications. Show less