title: Toxicity of neurons treated with herbicides and neuroprotection by mitochondria-targeted antioxidant SS31.
abstract: The purpose of this study was to determine the neurotoxicity of two commonly used herbicides: picloram and triclopyr and the neuroprotective effects of the mitochondria-targeted antioxidant, SS31. Using mouse neuroblastoma (N2a) cells and primary neurons from C57BL/6 mice, we investigated the toxicity of these herbicides, and protective effects of SS1 peptide against picloram and triclopyr toxicity. We measured total RNA content, cell viability and mRNA expression of peroxiredoxins, neuroprotective genes, mitochondrial-encoded electron transport chain (ETC) genes in N2a cells treated with herbicides and SS31. Using primary neurons from C57BL/6 mice, neuronal survival was studied in neurons treated with herbicides, in neurons pretreated with SS31 plus treated with herbicides, neurons treated with SS31 alone, and untreated neurons. Significantly decreased total RNA content, and cell viability in N2a cells treated with picloram and triclopyr were found compared to untreated N2a cells. Decreased mRNA expression of neuroprotective genes, and ETC genes in cells treated with herbicides was found compared to untreated cells. Decreased mRNA expression of peroxiredoxins 1-6 in N2a cells treated with picloram was found, suggesting that picloram affects the antioxidant enzymes in N2a cells. Immunofluorescence analysis of primary neurons revealed that decreased neuronal branching and degenerating neurons in neurons treated with picloram and triclopyr. However, neurons pretreated with SS31 prevented degenerative process caused by herbicides. Based on these results, we propose that herbicides--picloram and triclopyr appear to damage neurons, and the SS31 peptide appears to protect neurons from herbicide toxicity.
authors.affiliation: Neurogenetics Laboratory, Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA. tejaswinireddy99@gmail.com
authors.forename: Tejaswini P
authors.initials: TP
authors.lastname: Reddy
authors.forename: Maria
authors.initials: M
authors.lastname: Manczak
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Calkins
authors.forename: Peizhong
authors.initials: P
authors.lastname: Mao
authors.forename: Arubala P
authors.initials: AP
authors.lastname: Reddy
authors.forename: Ulziibat
authors.initials: U
authors.lastname: Shirendeb
authors.forename: Byung
authors.initials: B
authors.lastname: Park
authors.forename: P Hemachandra
authors.initials: PH
authors.lastname: Reddy
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D045222:Electron Transport Chain Complex Proteins / Q000096:biosynthesis; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006016:Glycolates / Q000633:toxicity*; D006540:Herbicides / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D009842:Oligopeptides / Q000008:administration & dosage / Q000502:physiology*; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000096:biosynthesis; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010846:Picloram / Q000633:toxicity*; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000096:biosynthesis; D014157:Transcription Factors; D014158:Transcription, Genetic
chemical_list: D000975:Antioxidants; D045222:Electron Transport Chain Complex Proteins; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D006016:Glycolates; D006540:Herbicides; D009842:Oligopeptides; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D015534:Trans-Activators; D014157:Transcription Factors; C506540:arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide; D012313:RNA; D054464:Peroxiredoxins; C032742:triclopyr; D010846:Picloram