In Vitro Effect of H2O2, Some Transition Metals and Hydroxyl Radical Produced Via Fenton and Fenton-Like Reactions, on the Catalytic Activity of AChE and the Hydrolysis of ACh
In Vitro Effect of H2O2, Some Transition Metals and Hydroxyl Radical Produced Via Fenton and Fenton-Like Reactions, on the Catalytic Activity of AChE and the Hydrolysis of ACh
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DOI：
10.1007/s11064-014-1400-5
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发表时间：
2014-11-01
影响因子：
4.4
通讯作者：
Cecilia Rosales-Hernandez, Martha
中科院分区：
文献类型：
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作者：
Mendez-Garrido, Armando;Hernandez-Rodriguez, Maricarmen;Cecilia Rosales-Hernandez, Martha
众所周知，阿尔茨海默病（AD）涉及的主要生物分子是乙酰胆碱酯酶（AChE）、乙酰胆碱（ACh）以及由42个氨基酸残基组成的β - 淀粉样肽（Aβ42）。乙酰胆碱在人类记忆和学习中起着重要作用，但它容易被乙酰胆碱酯酶水解，而Aβ42的聚集会形成寡聚体和纤维，这些在大脑中形成老年斑。Aβ42寡聚体能够产生过氧化氢（H₂O₂），它与阿尔茨海默病患者大脑中高浓度存在的金属（Fe²⁺、Cu²⁺、Cr³⁺、Zn²⁺和Cd²⁺）发生反应，通过芬顿（FR）反应和类芬顿（FLR）反应产生羟基自由基（·OH）。这种机制产生大量自由基，进而产生氧化应激，这与阿尔茨海默病的产生和发展相关。因此，我们在体外研究了金属（Fe³⁺、Cu²⁺、Cr³⁺、Zn²⁺和Cd²⁺）、过氧化氢（无Aβ42）以及由芬顿反应和类芬顿反应产生的羟基自由基对乙酰胆碱酯酶催化活性和乙酰胆碱水平的影响。结果表明，过氧化氢和金属不会改变乙酰胆碱酯酶的催化活性，但羟基自由基会使其降低。另一方面，金属、过氧化氢和羟基自由基会增加乙酰胆碱的水解。这一发现表明，当存在过氧化氢、金属和羟基自由基时，乙酰胆碱酯酶的催化活性和乙酰胆碱水平都会降低。此外，未来研究当过氧化氢直接由Aβ42产生时是否会观察到这些效应可能会很有趣。
It is well known that the principal biomolecules involved in Alzheimer's disease (AD) are acetylcholinesterase (AChE), acetylcholine (ACh) and the amyloid beta peptide of 42 amino acid residues (A beta 42). ACh plays an important role in human memory and learning, but it is susceptible to hydrolysis by AChE, while the aggregation of A beta 42 forms oligomers and fibrils, which form senile plaques in the brain. The A beta 42 oligomers are able to produce hydrogen peroxide (H2O2), which reacts with metals (Fe2+, Cu2+, Cr3+, Zn2+, and Cd2+) present at high concentrations in the brain of AD patients, generating the hydroxyl radical (-OH) via Fenton (FR) and Fenton-like (FLR) reactions. This mechanism generates high levels of free radicals and, hence, oxidative stress, which has been correlated with the generation and progression of AD. Therefore, we have studied in vitro how AChE catalytic activity and ACh levels are affected by the presence of metals (Fe3+, Cu2+, Cr3+, Zn2+, and Cd2+), H2O2 (without A beta 42), and -OH radicals produced from FR and FLR. The results showed that the H2O2 and the metals do not modify the AChE catalytic activity, but the -OH radical causes a decrease in it. On the other hand, metals, H2O2 and -OH radicals, increase the ACh hydrolysis. This finding suggests that when H2O2, the metals and the -OH radicals are present, both, the AChE catalytic activity and ACh levels diminish. Furthermore, in the future it may be interesting to study whether these effects are observed when H2O2 is produced directly from A beta 42.