Jang, Wooyoung Kim, Hee Ju Li, Huan Jo, Kwang Deog Lee, Moon Kyu Song, Sun Hong Yang, Hyun Ok 2024-01-20T09:03:29Z 2024-01-20T09:03:29Z 2021-09-02 2014-08-15 0006-291X https://pubs.kist.re.kr/handle/201004/126465 Background and objectives: Dysregulation of the autophagy pathway has been suggested as an important mechanism in the pathogenesis of Parkinson's disease (PD). Therefore, modulation of autophagy may be a novel strategy for the treatment of PD. Recently, an active form of vitamin D-3 has been reported to have neuroprotective properties. Therefore, we investigated the protective, autophagy-modulating effects of 1,25-dyhydroxyvitamin D-3 (calcitriol) in an in vitro model of Parkinson's disease. Methods: An in vitro model of Parkinson's disease, the rotenone-induced neurotoxicity model in SH-SY5Y cells was adapted. We measured cell viability using an MTT assay, Annexin V/propidium iodide assay, and intracellular reactive oxygen species levels and analyzed autophagy-associated intracellular signaling proteins by Western blotting. Results: Rotenone treatment of SH-SY5Y cells reduced their viability. This treatment also increased reactive oxygen species levels and decreased levels of intracellular signaling proteins associated with cell survival; simultaneous exposure to calcitriol significantly reversed these effects. Additionally, calcitriol increased levels of autophagy markers, including LC3, beclin-1, and AMPK. Rotenone inhibited autophagy, as indicated by decreased beclin-1 levels and increased mTOR levels, and this effect was reversed by calcitriol treatment. Discussion: Calcitriol protects against rotenone-induced neurotoxicity in SH-SY5Y cells by enhancing autophagy signaling pathways such as those involving LC3 and beclin-1. These neuroprotective effects of calcitriol against rotenone-induced dopaminergic neurotoxicity provide an experimental basis for its clinical use in the treatment of PD. (C) 2014 Elsevier Inc. All rights reserved. English ACADEMIC PRESS INC ELSEVIER SCIENCE VITAMIN-D-RECEPTOR PARKINSON-DISEASE ALPHA-SYNUCLEIN PATHOGENESIS NEURONS NEUROPROTECTION DEGRADATION PREVALENCE MECHANISMS EXPRESSION 1,25-Dyhydroxyvitamin D-3 attenuates rotenone-induced neurotoxicity in SH-SY5Y cells through induction of autophagy Article 10.1016/j.bbrc.2014.07.081 1 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.451, no.1, pp.142 - 147 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 451 1 142 147 scie scopus 000340864200023 2-s2.0-84906217905 Biochemistry & Molecular Biology Biophysics Biochemistry & Molecular Biology Biophysics Article VITAMIN-D-RECEPTOR PARKINSON-DISEASE ALPHA-SYNUCLEIN PATHOGENESIS NEURONS NEUROPROTECTION DEGRADATION PREVALENCE MECHANISMS EXPRESSION Calcitriol Parkinson&apos s disease Autophagy Neuroprotection