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1,25-Dyhydroxyvitamin D₃ attenuates rotenone-induced neurotoxicity in SH-SY5Y cells through induction of autophagy.
Biochem Biophys Res Commun. 2014 Aug 15; 451(1):142-7.BB

Abstract

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 D₃ has been reported to have neuroprotective properties. Therefore, we investigated the protective, autophagy-modulating effects of 1,25-dyhydroxyvitamin D₃ (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.

Authors+Show Affiliations

Department of Neurology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Bangdong-ri, Sacheon-myeon, Gangneung-si, Gangwon-do 210-711, Republic of Korea. Electronic address: neveu@gnah.co.kr.Natural Medicine Center, Korea Institute of Science and Technology, Gangneung 210-340, Republic of Korea.Natural Medicine Center, Korea Institute of Science and Technology, Gangneung 210-340, Republic of Korea.Department of Neurology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Bangdong-ri, Sacheon-myeon, Gangneung-si, Gangwon-do 210-711, Republic of Korea.Department of Neurology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Bangdong-ri, Sacheon-myeon, Gangneung-si, Gangwon-do 210-711, Republic of Korea.Department of Rehabilitation Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Bangdong-ri, Sacheon-myeon, Gangneung-si, Gangwon-do 210-711, Republic of Korea.Natural Medicine Center, Korea Institute of Science and Technology, Gangneung 210-340, Republic of Korea. Electronic address: hoyang@kist.re.kr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25078626

Citation

Jang, Wooyoung, et al. "1,25-Dyhydroxyvitamin D₃ Attenuates Rotenone-induced Neurotoxicity in SH-SY5Y Cells Through Induction of Autophagy." Biochemical and Biophysical Research Communications, vol. 451, no. 1, 2014, pp. 142-7.
Jang W, Kim HJ, Li H, et al. 1,25-Dyhydroxyvitamin D₃ attenuates rotenone-induced neurotoxicity in SH-SY5Y cells through induction of autophagy. Biochem Biophys Res Commun. 2014;451(1):142-7.
Jang, W., Kim, H. J., Li, H., Jo, K. D., Lee, M. K., Song, S. H., & Yang, H. O. (2014). 1,25-Dyhydroxyvitamin D₃ attenuates rotenone-induced neurotoxicity in SH-SY5Y cells through induction of autophagy. Biochemical and Biophysical Research Communications, 451(1), 142-7. https://doi.org/10.1016/j.bbrc.2014.07.081
Jang W, et al. 1,25-Dyhydroxyvitamin D₃ Attenuates Rotenone-induced Neurotoxicity in SH-SY5Y Cells Through Induction of Autophagy. Biochem Biophys Res Commun. 2014 Aug 15;451(1):142-7. PubMed PMID: 25078626.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 1,25-Dyhydroxyvitamin D₃ attenuates rotenone-induced neurotoxicity in SH-SY5Y cells through induction of autophagy. AU - Jang,Wooyoung, AU - Kim,Hee Ju, AU - Li,Huan, AU - Jo,Kwang Deog, AU - Lee,Moon Kyu, AU - Song,Sun Hong, AU - Yang,Hyun Ok, Y1 - 2014/07/29/ PY - 2014/07/12/received PY - 2014/07/17/accepted PY - 2014/8/1/entrez PY - 2014/8/1/pubmed PY - 2014/12/15/medline KW - Autophagy KW - Calcitriol KW - Neuroprotection KW - Parkinson’s disease SP - 142 EP - 7 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 451 IS - 1 N2 - 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 D₃ has been reported to have neuroprotective properties. Therefore, we investigated the protective, autophagy-modulating effects of 1,25-dyhydroxyvitamin D₃ (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. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/25078626/125_Dyhydroxyvitamin_D₃_attenuates_rotenone_induced_neurotoxicity_in_SH_SY5Y_cells_through_induction_of_autophagy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(14)01323-0 DB - PRIME DP - Unbound Medicine ER -