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Effect of MLL modified H3K4me3 on aluminum induced cognitive impairment
Toxicology Letters 280S (2017) S82–S91
Contents lists available at ScienceDirect
Toxicology Letters journal homepage: www.elsevier.com/locate/toxlet
P01-01 Mechanicms of toxicity
POSTERS P-01-01-01 Effect of MLL modified H3K4me3 on aluminum induced cognitive impairment
P-01-01-02 Elevation of p-P53(S15) by cdk5 contributes to neuronal apoptosis after exposure to benzo[a]pyrene Ji Sheng Nie
Qiao Niu School of Public Health, Shanxi Medical University, Taiyuan, China Objective: Epigenetic modifications play critical roles in cognition. Brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity and may be modified by tri-methyl histone H3 lysine residues 4 points (H3K4me3), which may be modified by mixedlineage leukemia protein (MLL), a zinc finger-rich enzyme, thus affecting cognition. This study aims to explore mechanism of this epigenetic modification. Methods: 1. 235 male Al-exposed workers were recruited. An occupational epidemiological investigation questionnaire and cognitive tests were performed. The contents of H3K4me3 in lymphocyte and BDNF in plasma were determined by enzyme-linked immunosorbent assay. 2. 24 healthy SD male rats were randomly divided into four groups by weight. The rats drank water containing different doses of aluminum chloride (AlCl3 ) (0, 2, 12, and 72 mg/kg Al3+ ) for 120d. The neurobehavior of animals was tested, and expression of H3K4me2 and MLL was detected with western blot. Results: 1. With the increasing of blood aluminum level, the cognitive function of Al-exposed workers decreased, The expression levels of H3K4me3 decreased, and BDNF decreased. Multiple correlation analysis showed that Blood aluminum concentration was negatively correlated to H3K4me3, BDNF, and cognitive function, respectively. 2. With the Al dose increasing, the neurobehavior of animals decreased, the expression of MLL and H3K4me3 decreased too. Conclusion: Aluminum inhibits MLL by replacing zinc, then the activity of MLL decreases, the methylation of H3K4 increases, the expression of H3K4me3 increases, then BDNF decreases. This work is supported by NSFC 81430078, 81372968. http://dx.doi.org/10.1016/j.toxlet.2017.07.224
Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, China As a representative substance of the polycyclic aromatic hydrocarbons (PAH), benzo[a]pyrene (B[a]P) is a widely distributed environmental contaminant. Exposure to B[a]P can take place by ingestion of contaminated (especially grilled, roasted or smoked) food or water, or inhalation of polluted air. Several studies have indicated that B[a]P exposure could impair learning and memory function on human population and animal models. Neuronal apoptosis plays a crucial role in neurodegenerative diseases manifesting deficits of learning and memory. In the present study, We utilized both in vivo and in vitro systems to demonstrate that B[a]P causes neuronal apoptosis. Using primary cortical neuronal culture, we showed for the first time that B[a]P administration results in elevation of expression of p25, p35 and cdk5 within the neuron thereby causing increase of cdk5 activity resulting in increased p53 phosphorylation at Ser15 from the cells. All these factors contributed to apopotic death of cortical neurons in vitro. When administered to SD rats, B[a]P was found to cause neuronal apoptosis and elevation of expression of p35, p25, cdk5 and Ser15 p53 phosphorylation in the cortex in a time and dose dependent manner. Our results show elevation of p-P53(S15) by Cdk5 contributes to cortical neuronal apoptosis after exposure to benzo[a]pyrene, implying that B[a]P may play a role in the neurodegenerative processes. http://dx.doi.org/10.1016/j.toxlet.2017.07.225 P-01-01-03 Biperiden is an inhibitor of acetylcholinesterase 2 , Miroslav Pohanka 1 ˇ Adam Kostelník 1,2 , Alexander Cegan 1 2
University of Defence, Hradec Králové, Czech Republic University of Pardubice, Pardubice, Czech Republic
Biperiden is used in treatment of Parkinson disease and as anticonvulsive compound in poisoning by organophosphates; it is antagonist of muscarinic receptor. While acetylcholinesterase 0378-4274/
Contents lists available at ScienceDirect
Toxicology Letters journal homepage: www.elsevier.com/locate/toxlet
P01-01 Mechanicms of toxicity
POSTERS P-01-01-01 Effect of MLL modified H3K4me3 on aluminum induced cognitive impairment
P-01-01-02 Elevation of p-P53(S15) by cdk5 contributes to neuronal apoptosis after exposure to benzo[a]pyrene Ji Sheng Nie
Qiao Niu School of Public Health, Shanxi Medical University, Taiyuan, China Objective: Epigenetic modifications play critical roles in cognition. Brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity and may be modified by tri-methyl histone H3 lysine residues 4 points (H3K4me3), which may be modified by mixedlineage leukemia protein (MLL), a zinc finger-rich enzyme, thus affecting cognition. This study aims to explore mechanism of this epigenetic modification. Methods: 1. 235 male Al-exposed workers were recruited. An occupational epidemiological investigation questionnaire and cognitive tests were performed. The contents of H3K4me3 in lymphocyte and BDNF in plasma were determined by enzyme-linked immunosorbent assay. 2. 24 healthy SD male rats were randomly divided into four groups by weight. The rats drank water containing different doses of aluminum chloride (AlCl3 ) (0, 2, 12, and 72 mg/kg Al3+ ) for 120d. The neurobehavior of animals was tested, and expression of H3K4me2 and MLL was detected with western blot. Results: 1. With the increasing of blood aluminum level, the cognitive function of Al-exposed workers decreased, The expression levels of H3K4me3 decreased, and BDNF decreased. Multiple correlation analysis showed that Blood aluminum concentration was negatively correlated to H3K4me3, BDNF, and cognitive function, respectively. 2. With the Al dose increasing, the neurobehavior of animals decreased, the expression of MLL and H3K4me3 decreased too. Conclusion: Aluminum inhibits MLL by replacing zinc, then the activity of MLL decreases, the methylation of H3K4 increases, the expression of H3K4me3 increases, then BDNF decreases. This work is supported by NSFC 81430078, 81372968. http://dx.doi.org/10.1016/j.toxlet.2017.07.224
Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, China As a representative substance of the polycyclic aromatic hydrocarbons (PAH), benzo[a]pyrene (B[a]P) is a widely distributed environmental contaminant. Exposure to B[a]P can take place by ingestion of contaminated (especially grilled, roasted or smoked) food or water, or inhalation of polluted air. Several studies have indicated that B[a]P exposure could impair learning and memory function on human population and animal models. Neuronal apoptosis plays a crucial role in neurodegenerative diseases manifesting deficits of learning and memory. In the present study, We utilized both in vivo and in vitro systems to demonstrate that B[a]P causes neuronal apoptosis. Using primary cortical neuronal culture, we showed for the first time that B[a]P administration results in elevation of expression of p25, p35 and cdk5 within the neuron thereby causing increase of cdk5 activity resulting in increased p53 phosphorylation at Ser15 from the cells. All these factors contributed to apopotic death of cortical neurons in vitro. When administered to SD rats, B[a]P was found to cause neuronal apoptosis and elevation of expression of p35, p25, cdk5 and Ser15 p53 phosphorylation in the cortex in a time and dose dependent manner. Our results show elevation of p-P53(S15) by Cdk5 contributes to cortical neuronal apoptosis after exposure to benzo[a]pyrene, implying that B[a]P may play a role in the neurodegenerative processes. http://dx.doi.org/10.1016/j.toxlet.2017.07.225 P-01-01-03 Biperiden is an inhibitor of acetylcholinesterase 2 , Miroslav Pohanka 1 ˇ Adam Kostelník 1,2 , Alexander Cegan 1 2
University of Defence, Hradec Králové, Czech Republic University of Pardubice, Pardubice, Czech Republic
Biperiden is used in treatment of Parkinson disease and as anticonvulsive compound in poisoning by organophosphates; it is antagonist of muscarinic receptor. While acetylcholinesterase 0378-4274/