Loss of function mutations of DJ-1 (PARK7) have been linked to the pathogenesis of Parkinson disease (PD). Antioxidative stress is one of the multi-protective functions of DJ-1, and oxidation of cysteine 106 (Cys106) has been proposed to regulate the protective activity of DJ-1. Uncoupling protein 4 (UCP4) is located in the inner membrane of mitochondria and functions to protect against oxidative stress. In this study, we used neuronal (SH-SY5Y) cells and DJ-1 knockout (KO) mice to elucidate whether DJ-1 regulated oxidative stress via modulating the expression of UCP4, and the underlying mechanism. The downstream products of oxidative stress, mitochondrial membrane potential (ΔΨm) and cell viability were also investigated. We found that UCP4 was up regulated upon 1-methyl-4-phenylpyridinium (MPP+) stimulation in SH-SY5Y cells, which was enhanced by wild type DJ-1 and alleviated by DJ-1 knockdown. Expression of UCP4 in DJ-1 KO mice was lower compared with wild type mice. In addition, up-regulation of UCP4 was alleviated by inhibition of oxidized DJ-1, and enhanced by increase of oxidized DJ-1 under conditions of oxidative stress using western blot analysis. Moreover, overexpression of UCP4 in DJ-1 knockdown cells partially reversed the decrease of cell viability, ΔΨm, as well as the increase of products of oxidative stress upon MPP+ stimulation. Further analysis showed that DJ-1 regulated transcriptional activity of UCP4 partially via Nuclear factor-kappa B (NF-κB) pathway in the presence of MPP+. Together, our results suggested DJ-1 might regulate the expression of UCP4 by oxidation of DJ-1 and partially via NF-κB pathway in its protective response to oxidative stress.
In this video from TIME, learn about the evolution of Parkinson’s disease treatment since the late 1950s. Vice president of media communications for the Michael J.… (weiter lesen)
Dementia affects millions of people worldwide, robbing them of their ability to think, remember and live as they once did. In the search for… (weiter lesen)
Summary: a review of the eight top videos on the future of medicine reported in 2017. [This article first appeared on the LongevityFacts.com website. Author: Brady Hartman.]… (weiter lesen)
Summary: A disease-modifying drug for Parkinson’s disease remains the goal of researchers as they develop promising treatments using gene therapy, autophagy upregulators, and brain… (weiter lesen)
In a new study, researchers at the ASU-Banner Neurodegenerative Disease Research Center examine the effects of Alzheimer’s disease on the functioning of mitochondria–structures performing… (weiter lesen)