Biological Neurotoxicity Evaluationand Mechanism Analysisof Typical Polybrominated Diphenyl Ethers In Environment

Polybrominated diphenyl ethers(PBDEs)are widely used in all areas of production and life,which inevitably enter the environment.2,2',4,4'-tetrabromodiphenyl ether(BDE-47)and 2,2',3,3',4,4',5,5',6,6'-decabromobiphenyl ether(BDE-209)is more widely used and is often detected in the environment.PBDEs are neurotoxic to organisms,but their mechanism is not clear.Acetylcholinesterase(AChE),as one of the important enzymes in the nervous system,plays an important role in the process of information transmission and value differentiation of nerve cells.Any substance that affects AChE activity may lead to neurotoxicity.In this paper,BDE-47 and BDE-209 were used to study the inhibitory properties of ACh E and AChE.The effects of BDE-47 and BDE-209 and AChE were studied by spectroscopic technique and molecular docking technique.The mechanism of interaction was analyzed to elucidate one of the toxic pathways that caused neurotoxicity due to the effect of AChE.BDE-47 and BDE-209 can inhibit the decomposition of acetylcholine by AChE in a certain concentration range.With the increase of the concentration,the inhibition rates of both BDE-47 and BDE-209 increased first and then decreased.When the concentration of BDE-47 is 400umol/L,the inhibition rate is 22.3%.When the concentration of BDE-209 is 200umol/L,the inhibition rate is 11.2%.The results of UV spectroscopy show that both BDE-47 and BDE-209 can affect the aromatic amino acids in AChE,and BDE-47 and BDE-209 can redistribute the absorption peak of AChE.The UV absorption of BDE-47 and AChE mixtures and BDE-209 and AChE mixtures increases significantly at about 260 and 280 nm,indicating that BDE-47 and BDE-209 are likely to alter the microenvironment of some amino acid residues of AChE and leading to changes in the AChE conformation.The results of fluorescence spectroscopy show that BDE-47 and BDE-209 change the microenvironment around the amino acid residues in AChE,making it more hydrophobic.BDE-47 and BDE-209 have a certain quenching effect on AChE fluorescence,and their quenching types are static quenching.The interaction of BDE-47 and BDE-209 with AChE mainly exist hydrophobic,and there is a certain electrostatic effect,there is no van der Waals interaction and hydrogen bonding.The intermolecular distances between BDE-47 with AChE and BDE-209 with AChE are 1.9 nm and 2.0 nm,respectively,indicating that energy migration occurres.The results of molecular docking show that the binding energies of BDE-47 and BDE-209 with AChE are-32.6kJ/mol and-24.7 kJ/mol,respectively.The interaction of BDE-47 and BDE-209 with AChE mainly includes hydrophobic interaction and electrostatic interaction,and there is no hydrogen bond.The key amino acid residues of BDE-47 interacting with AChE may be TRP-83 and TYR-180.The key amino acid residues of BDE-209 interacting with AChE may be TRP-321 and TYR-324.The inhibitory rate of ACDE activity is higher than that of BDE-209,and the binding constants of BDE-47 and AChE are higher than those of BDE-209 and AChE,and the binding constant is decreased with the increase of temperature.The binding distance between BDE-47 and AChE is less than that of BDE-209 and AChE.The interaction between BDE-47 and AChE is also higher than that of BDE-209 and AChE.Those demonstrate that BDE-47 is more likely to bind to AChE than BDE-209,and that the increase of temperature is not conducive to the interaction of BDE-47 and BDE-209 with AChE.