Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-019, Lisbon, Portugal
Dr. Rita Guedes
Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-019, Lisbon, Portugal
The hydration of the hydroxyl OH radical has been investigated by microsolvation modeling and statistical mechanics Monte Carlo simulations. The microsolvation approach was based on density functional theory (DFT) calculations for and clusters. The results from microsolvation indicate that the binding enthalpies of the OH radical and water molecule to small water clusters are similar. Monte Carlo simulations predict that the hydration enthalpy of the OH radical, is −39.1 kJ mol−1. From this value we have estimated that the band gap of liquid water is 6.88 eV, which is in excellent agreement with the result of Coe et al. [J. Chem. Phys. 107, 6023 (1997)]. We have compared the structure of the hydrated OH solution with the structure of pure liquid water. The structural differences between the two systems reflect the strong role played by the OH radical as a proton donor in water. From sequential Monte Carlo/DFT calculations the dipole moment of the OH radical in liquid water is which is ∼33% above the experimental gas phase value (1.66 D).
1 June 2014 in European Journal of Medicinal Chemistry
Oxidative stress is a key pathological feature of Parkinson's disease (PD). GlutathioneS‐transferase pi (GSTP) is a neuroprotective antioxidant enzyme regulated at the transcriptional level by the antioxidant master regulator nuclear factor‐erythroid 2‐related factor 2 (Nrf2). Here, we show for the first time that upon MPTP‐induced oxidative stress, GSTP potentiatesS‐glutathionylation of Kelch‐like ECH‐associated protein 1 (Keap1), an endogenous repressor of Nrf2,in vivo.S‐glutathionylation of Keap1 leads to Nrf2 activation and subsequently increases expression of GSTP. This positive feedback regulatory loop represents a novel mechanism by which GSTP elicits antioxidant protection in the brain.