Prolyl oligopeptidase inhibition reduces oxidative stress via reducing NADPH oxidase activity by activating protein phosphatase 2A.

Oxidative stress (OS) is a common toxic feature in various neurodegenerative diseases. Therefore, reducing OS could provide a potential approach to achieve neuroprotection. Prolyl oligopeptidase (PREP) is a serine protease that is linked to neurodegeneration, as endogenous PREP inhibits autophagy and induces the accumulation of detrimental protein aggregates. As such, inhibition of PREP by a small-molecular inhibitor has provided neuroprotection in preclinical models of neurodegenerative diseases. In addition, PREP inhibition has been shown to reduce production of reactive oxygen species (ROS) and the absence of PREP blocks stress-induced ROS production. However, the mechanism behind PREP-related ROS regulation is not known. As we recently discovered PREP's physiological role as a protein phosphatase 2A (PP2A) regulator, we wanted to characterize PREP inhibition as an approach to reduce OS. We studied the impact of a PREP inhibitor, KYP-2047, on hydrogen peroxide and ferrous chloride induced ROS production and on cellular antioxidant response in HEK-293 and SH-SY5Y cells. In addition, we used HEK-293 and SH-SY5Y PREP knock-out cells to validate the role of PREP on stress-induced ROS production. We were able to show that absence of PREP almost entirely blocks the stress-induced ROS production in both cell lines. Reduced ROS production and smaller antioxidant response was also seen in both cell lines after PREP inhibition by 10 µM KYP-2047. Our results also revealed that the OS reducing mechanism of PREP inhibition is related to reduced activation of ROS producing NADPH oxidase through enhanced PP2A activation. In conclusion, our results suggest that PREP inhibition could also provide neuroprotection by reducing OS, thus broadening the scope of its beneficial effects on neurodegeneration.

The influence of an electrostatic precipitator and a mechanical filter on Rn decay products.

In the present work the effect of an HEPA filter and an electrostatic precipitator on the behaviour of Rn decay products has been studied in laboratory conditions. Both filters were found to decrease the equilibrium factor of progeny and increase the unattached fraction of decay products. In a clean air they also decreased the activity of unattached progeny. An electrostatic precipitator was found to produce condensation nuclei which were observable when no other particle sources were present. The ozone produced by the corona discharge of the filter probably has a great effect on the production of these submicron particles. The impurities of the air were found to grow the particles and thus their influence on the behaviour of Rn decay products became in some cases significant.

The control of radon progeny by air treatment devices.

The effect of air treatment devices on the behaviour of radon decay products has been studied in laboratory conditions. An HEPA filter and an electrostatic precipitator were used. Both of the filters were found to decrease the equilibrium factor of daughters and increase the unattached fraction of decay products. In a clean air they also decreased the activity of unattached daughters. The effect of the devices on the health risk caused by radon progeny was estimated by dosimetric calculations. The results corresponding to different models show considerable discrepancy, mainly due to different assumptions about the influence of unattached decay products on the dose.