Enrica Presta
Consiglio Nazionale delle Ricerche (CNR), Water Research Insitute (IRSA), Department Member
9-Hydroxystearic acid (9-HSA) belongs to the endogenous lipid peroxidation by-products that decrease in tumors, causing as a consequence the loss of one of the control mechanisms on cell division. It acts as a histone deacetylase (HDAC,... more
9-Hydroxystearic acid (9-HSA) belongs to the endogenous lipid peroxidation by-products that decrease in tumors, causing as a consequence the loss of one of the control mechanisms on cell division. It acts as a histone deacetylase (HDAC, E.C 3.5.1.98) inhibitor, and the interaction of the two enantiomers of 9-HSA with the catalytic site of the enzyme, investigated by using a molecular modelling approach, has been reported to be different. In this work we tested out this prediction by synthesizing the two enantiomers (R)-9-HSA (R-9) and (S)-9-HSA (S-9) starting from the natural source methyl dimorphecolate obtained from Dimorphotheca sinuata seeds and investigating their biological activity in HT29 cells. Both enantiomers inhibit the enzymatic activity of HDAC1, HDAC2 and HDAC3, R-9 being more active; R-9 and S-9 inhibitory effect induces an increase in histone H4 acetylation. We also demonstrate that the antiproliferative effect brought about by R-9 is more pronounced as well as we observe increase of p21 transcription and protein content, while the expression of cyclin D1 is decreased. Starting from these observations it can be hypothesized that the interaction of R-9 with HDAC1 induce conformational changes in the enzyme causing loss of its interaction with other proteins, like cyclin D1 itself.
Research Interests:
This study presents the proof-of-concept of the "Oil-Spill Snorkel": a novel bioelectrochemical approach to stimulate the oxidative biodegradation of... more
This study presents the proof-of-concept of the "Oil-Spill Snorkel": a novel bioelectrochemical approach to stimulate the oxidative biodegradation of petroleum hydrocarbons in sediments. The "Oil-Spill Snorkel" consists of a single conductive material (the snorkel) positioned suitably to create an electrochemical connection between the anoxic zone (the contaminated sediment) and the oxic zone (the overlying O2-containing water). The segment of the electrode buried within the sediment plays a role of anode, accepting electrons deriving from the oxidation of contaminants. Electrons flow through the snorkel up to the part exposed to the aerobic environment (the cathode), where they reduce oxygen to form water. Here we report the results of lab-scale microcosms setup with marine sediments and spiked with crude oil. Microcosms containing one or three graphite snorkels and controls (snorkel-free and autoclaved) were monitored for over 400 days. Collectively, the results of this study confirmed that the snorkels accelerate oxidative reactions taking place within the sediment, as documented by a significant 1.7-fold increase (p = 0.023, two-tailed t-test) in the cumulative oxygen uptake and 1.4-fold increase (p = 0.040) in the cumulative CO2 evolution in the microcosms containing three snorkels compared to snorkel-free controls. Accordingly, the initial rate of total petroleum hydrocarbons (TPH) degradation was also substantially enhanced. Indeed, while after 200 days of incubation a negligible degradation of TPH was noticed in snorkel-free controls, a significant reduction of 12 ± 1% (p = 0.004) and 21 ± 1% (p = 0.001) was observed in microcosms containing one and three snorkels, respectively. Although, the "Oil-Spill Snorkel" potentially represents a groundbreaking alternative to more expensive remediation options, further research efforts are needed to clarify factors and conditions affecting the snorkel-driven biodegradation processes and to identify suitable configurations for field applications.