title: Docosahexaenoic acid prevents paraquat-induced reactive oxygen species production in dopaminergic neurons via enhancement of glutathione homeostasis.
abstract: Omega-3 polyunsaturated fatty acid levels are reduced in the substantia nigra area in Parkinson's disease patients and animal models, implicating docosahexaenoic acid (DHA) as a potential treatment for preventing Parkinson's disease and suggesting the need for investigations into how DHA might protect against neurotoxin-induced dopaminergic neuron loss. The herbicide paraquat (PQ) induces dopaminergic neuron loss through the excessive production of reactive oxygen species (ROS). We found that treatment of dopaminergic SN4741 cells with PQ reduced cell viability in a dose-dependent manner, but pretreatment with DHA ameliorated the toxic effect of PQ. To determine the toxic mechanism of PQ, we measured intracellular ROS content in different organelles with specific dyes. As expected, all types of ROS were increased by PQ treatment, but DHA pretreatment selectively decreased cytosolic hydrogen peroxide content. Furthermore, DHA treatment-induced increases in glutathione reductase and glutamate cysteine ligase modifier subunit (GCLm) mRNA expression were positively correlated with glutathione (GSH) content. Consistent with this increase in GCLm mRNA levels, Western blot analysis revealed that DHA pretreatment increased nuclear factor-erythroid 2 related factor 2 (Nrf2) protein levels. These findings indicate that DHA prevents PQ-induced neuronal cell loss by enhancing Nrf2-regulated GSH homeostasis.
authors.affiliation: Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Hyoung Jun
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Jeongsu
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Yunseon
authors.initials: Y
authors.lastname: Jang
authors.affiliation: Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Soo Jeong
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Kang Sik
authors.initials: KS
authors.lastname: Seo
authors.affiliation: Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, Republic of Korea; Infection Signaling Network Research Center, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Soyeon
authors.initials: S
authors.lastname: Jeong
authors.affiliation: Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, Republic of Korea; Infection Signaling Network Research Center, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Soyeon
authors.initials: S
authors.lastname: Shin
authors.affiliation: Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, Republic of Korea; Infection Signaling Network Research Center, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Kyu
authors.initials: K
authors.lastname: Lim
authors.affiliation: Brainscience Institute, Chungnam National University, Daejeon, Republic of Korea. Electronic address: junyoung3@gmail.com.
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Heo
authors.affiliation: Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, Republic of Korea; Infection Signaling Network Research Center, Chungnam National University, Daejeon, Republic of Korea. Electronic address: mitochondria@cnu.ac.kr.
authors.forename: Gi Ryang
authors.initials: GR
authors.lastname: Kweon
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D010269:Paraquat / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D004281:Docosahexaenoic Acids; D005980:Glutathione Reductase; D005978:Glutathione; D010269:Paraquat
keywords: Docosahexaenoic acid; Glutathione homeostasis; Paraquat; Parkinson’s disease