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Use of human neuroblastoma SH-SY5Y cells to evaluate glyphosate-induced effects on oxidative stress, neuronal development and cell death signaling pathways
Highlights Cytotoxicity and neurotoxicity of glyphosate and AMPA in SH-SY5Y cells. Glyphosate and AMPA decrease MTT cell viability and increased LDH leakage. Glyphosate and AMPA increase MDA, NO and ROS production, and caspase-3/7 activity. Glyphosate and AMPA affect neuronal development related gene transcriptions. Glyphosate and AMPA affect gene expression profiling of cell death pathways.
Abstract Glyphosate-containing herbicides are the most used agrochemicals in the world. Their indiscriminate application raises some concerns regarding the possible health and environmental hazards. In this study, we investigated in human neuroblastoma cell line SH-SY5Y if oxidative stress, altered neurodevelopment and cell death pathways are involved in response to glyphosate and its metabolite aminomethylphosphonic acid (AMPA) exposures. MTT and LDH assays were carried out to assess the glyphosate and AMPA cytotoxicity. Lipid peroxides measured as malondialdehyde (MDA), nitric oxide (NO) and reactive oxygen species (ROS) production, and caspase-Glo 3/7 activity were evaluated. The neuroprotective role of melatonin (MEL), Trolox, N-acetylcysteine (NAC) and Sylibin against glyphosate- and AMPA-induced oxidative stress was examined. Glyphosate and AMPA effects on neuronal development related gene transcriptions, and gene expression profiling of cell death pathways by Real-Time PCR array were also investigated. Glyphosate (5 mM) and AMPA (10 mM) induced a significant increase in MDA levels, NO and ROS production and caspase 3/7 activity. Glyphosate exposure induced up-regulation of Wnt3a, Wnt5a, Wnt7a, CAMK2A, CAMK2B and down-regulation of GAP43 and TUBB3 mRNA expression involved in normal neural cell development. In relation to gene expression profiling of cell death pathways, of the 84 genes examined in cells a greater than 2-fold change was observed for APAF1, BAX, BCL2, CASP3, CASP7, CASP9, SYCP2, TNF, TP53, CTSB, NFκB1, PIK3C3, SNCA, SQSTMT, HSPBAP1 and KCNIPI mRNA expression for glyphosate and AMPA exposures. These gene expression data can help to define neurotoxic mechanisms of glyphosate and AMPA. Our results demonstrated that glyphosate and AMPA induced cytotoxic effects on neuronal development, oxidative stress and cell death via apoptotic, autophagy and necrotic pathways and confirmed that glyphosate environmental exposure becomes a concern. This study demonstrates that SH-SY5Y cell line could be considered an in vitro system for pesticide screening.
Use of human neuroblastoma SH-SY5Y cells to evaluate glyphosate-induced effects on oxidative stress, neuronal development and cell death signaling pathways
Highlights Cytotoxicity and neurotoxicity of glyphosate and AMPA in SH-SY5Y cells. Glyphosate and AMPA decrease MTT cell viability and increased LDH leakage. Glyphosate and AMPA increase MDA, NO and ROS production, and caspase-3/7 activity. Glyphosate and AMPA affect neuronal development related gene transcriptions. Glyphosate and AMPA affect gene expression profiling of cell death pathways.
Abstract Glyphosate-containing herbicides are the most used agrochemicals in the world. Their indiscriminate application raises some concerns regarding the possible health and environmental hazards. In this study, we investigated in human neuroblastoma cell line SH-SY5Y if oxidative stress, altered neurodevelopment and cell death pathways are involved in response to glyphosate and its metabolite aminomethylphosphonic acid (AMPA) exposures. MTT and LDH assays were carried out to assess the glyphosate and AMPA cytotoxicity. Lipid peroxides measured as malondialdehyde (MDA), nitric oxide (NO) and reactive oxygen species (ROS) production, and caspase-Glo 3/7 activity were evaluated. The neuroprotective role of melatonin (MEL), Trolox, N-acetylcysteine (NAC) and Sylibin against glyphosate- and AMPA-induced oxidative stress was examined. Glyphosate and AMPA effects on neuronal development related gene transcriptions, and gene expression profiling of cell death pathways by Real-Time PCR array were also investigated. Glyphosate (5 mM) and AMPA (10 mM) induced a significant increase in MDA levels, NO and ROS production and caspase 3/7 activity. Glyphosate exposure induced up-regulation of Wnt3a, Wnt5a, Wnt7a, CAMK2A, CAMK2B and down-regulation of GAP43 and TUBB3 mRNA expression involved in normal neural cell development. In relation to gene expression profiling of cell death pathways, of the 84 genes examined in cells a greater than 2-fold change was observed for APAF1, BAX, BCL2, CASP3, CASP7, CASP9, SYCP2, TNF, TP53, CTSB, NFκB1, PIK3C3, SNCA, SQSTMT, HSPBAP1 and KCNIPI mRNA expression for glyphosate and AMPA exposures. These gene expression data can help to define neurotoxic mechanisms of glyphosate and AMPA. Our results demonstrated that glyphosate and AMPA induced cytotoxic effects on neuronal development, oxidative stress and cell death via apoptotic, autophagy and necrotic pathways and confirmed that glyphosate environmental exposure becomes a concern. This study demonstrates that SH-SY5Y cell line could be considered an in vitro system for pesticide screening.
Use of human neuroblastoma SH-SY5Y cells to evaluate glyphosate-induced effects on oxidative stress, neuronal development and cell death signaling pathways
Martínez, María-Aránzazu (author) / Rodríguez, José-Luis (author) / Lopez-Torres, Bernardo (author) / Martínez, Marta (author) / Martínez-Larrañaga, María-Rosa (author) / Maximiliano, Jorge-Enrique (author) / Anadón, Arturo (author) / Ares, Irma (author)
2019-12-10
Article (Journal)
Electronic Resource
English
Glyphosate , Neurotoxicity , SH-SY5Y cells , Oxidative stress , Cell death pathways , Risk factors , ABL1 , C-abl oncogene 1, non-receptor tyrosine kinase , AKT1 , V-akt murine thymoma viral oncogene homolog 1 , AMPA , Aminomethylphosphonic acid , APAF1 , Apoptotic peptidase activating factor 1 , APP , Amyloid beta (A4) precursor protein , ATG12 , ATG12 autophagy related 12 homolog (S. cerevisiae) , ATG3 , ATG3 autophagy related 3 homolog (S. cerevisiae) , ATG5 , ATG5 autophagy related 5 homolog (S. cerevisiae) , BAX , BCL2-associated X protein , BCL2 , B-cell CLL/lymphoma 2 , BCL2A1 , BCL2-related protein A1 , BCL2L11 , BCL2-like 11 (apoptosis facilitator) , BIRC2 , Baculoviral IAP repeat containing 2 , CAMK2A , Calcium/calmodulin-dependent protein kinase II alpha , CAMK2B , Calcium/calmodulin dependent protein kinase II beta , CASP1 , Caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) , CASP3 , Caspase 3, apoptosis-related cysteine peptidase , CASP6 , Caspase 6, apoptosis-related cysteine peptidase , CASP7 , Caspase 7, apoptosis-related cysteine peptidase , CASP9 , Caspase 9, apoptosis-related cysteine peptidase , CD40 , CD40 molecule, TNF receptor superfamily member 5 , CD40LG , CD40 ligand , cDNA , Complementary DNA , CFLAR , CASP8 and FADD-like apoptosis regulator , CNS , Central nervous system , Ct , Cycle threshold , CTSB , Cathepsin B , CYLD , Cylindromatosis (turban tumor syndrome) , DAF-2 , 4,5-diaminofluorescein , DAF-2 DA , 4,5-diaminofluorescein diacetate , DAF-2T , Triazolofluorescein , DAF-FM , 4 amino-5-methylamino-2′,7′-difluorescein , DAF-FM-DA , 4 amino-5-methylamino-2′,7′-difluorescein diacetate , DCFH , 2,7-dichlorofluorescein , DCFH-DA , 2,7-dichlorofluorescein diacetate , DENND4A , DENN/MADD domain containing 4A , DMEM F-12 , Dulbecco's modified eagle medium:F12 , DMSO , Dimethyl sulfoxide , DPBS , Dulbecco’s phosphate buffered saline , EIF5B , Eukaryotic translation initiation factor 5B , FAS , Fas (TNF receptor superfamily, member 6) , FASLG , Fas ligand (TNF superfamily, member 6) , FBS , Fetal bovine serum , FOXI1 , Forkhead box I1 , GADD45A , Growth arrest and DNA-damage-inducible, alpha , GALNT5 , UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 5 (GalNAc-T5) , GAP43 , Growth-associated protein 43 , GAPDH , Glyceraldehyde-3-phosphate dehydrogenase , HSPBAP1 , HSPB (heat shock 27kDa) associated protein 1 , IFNG , Interferon, gamma , IGF1 , Insulin-like growth factor 1 (somatomedin C) , IL6 , Interleukin 6 , INS , Insulin , IPA , Ingenuity Pathway Analysis Tool , IPKB , Ingenuity Pathway Knowledge Base , IRGM , Immunity-related GTPase family, M , KCNIP1 , Potassium channel interacting protein 1 , LD<inf>50</inf> , Lethal dose for 50% of test animals , LDH , Lactate dehydrogenase , MAPK8 , Mitogen-activated protein kinase 8 , MCL1 , Myeloid cell leukemia sequence 1 (BCL2-related) , MDA , Malondialdehyde tetrabutylammonium salt , MEL , Melatonin , mRNA , Messenger RNA , MTT , 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide , NAC , N-acetylcysteine , NFκB1 , Nuclear transcription factor kappa B subunit 1 , NO , Nitric oxide , NOL3 , Nucleolar protein 3 (apoptosis repressor with CARD domain) , OR10J3 , Olfactory receptor, family 10, subfamily J, member 3 , PARP2 , Poly (ADP-ribose) polymerase 2 , PCR , Polymerase chain reaction , PIK3C3 , Phosphoinositide-3-kinase, class 3 , RAB25 , RAB25, member RAS oncogene family , ROS , Reactive oxygen species , RPS6KB1 , Ribosomal protein S6 kinase, 70kDa, polypeptide 1 , S100A7A , S100 calcium binding protein A7A , SEM , Standard error of the mean , SH-SY5Y , Human neuroblastoma cell line , SNCA , Synuclein, alpha (non A4 component of amyloid precursor) , SQSTM1 , Sequestosome 1 , SYCP2 , Synaptonemal complex protein 2 , TBA , Thiobarbituric acid , TBARS , Thiobarbituric acid reactive substance , TMEM57 , Transmembrane protein 57 , TNF , Tumor necrosis factor , TNFRSF11B , Tumor necrosis factor receptor superfamily, member 11b , TNFα , Tumor necrosis factor-α , TP53 , Tumor protein p53 , TUBB3 , Tubulin beta 3 class III , Wnt3a , Wnt family member 3A , Wnt5a , Wnt family member 5A , Wnt7a , Wnt family member 7A , XIAP , X-linked inhibitor of apoptosis
British Library Online Contents | 2017