PON1 and PON3 in Alzheimer's Disease: Similar Functions but Different Roles.

IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Alessandro Trentini, Valentina Rosta, Raffaella Riccetti, Gianmarco Mola, Riccardo Galletti, Marco Pinotti, Vincenza Senia, Giovanni Zuliani, Carlo Cervellati
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Abstract

Paraoxonase 1 (PON1) and Paraoxonase 3 (PON3) are enzymes located on the surface of high-density lipoprotein (HDL) and share similar antioxidant properties, possibly modulated by other proteins such as Myeloperoxidase (MPO), which drives the shift from functional to dysfunctional HDL. PON1 has been extensively studied in relation to Alzheimer's Disease (AD), but the role of PON3 remains unknown. To fill this knowledge gap, the study analyzed PON3 protein levels and PON1-arylesterase activity in 99 AD patients, 100 patients with mild cognitive impairment (MCI), and 79 cognitively normal controls. The results showed that serum PON3 levels remained unchanged across all groups. In contrast, serum arylesterase activity was significantly reduced in both AD and MCI patients compared to controls (p < 0.001 for both comparisons). Surprisingly, there was no correlation between arylesterase activity and MPO protein concentration or activity. However, PON3 was found to have a significant positive correlation with both MPO concentration (r = 0.507, p < 0.0001) and MPO activity (r = 0.264, p < 0.01). In conclusion, we demonstrated for the first time that PON1 and PON3 have distinct relationships with AD, with only PON1 showing a decrease in activity in this disease, while PON3 levels remained unchanged. Another noteworthy finding was the selective correlation between PON3 and MPO, which may suggest a preferential physical association of PON3 with dysfunctional HDL.

阿尔茨海默病中的 PON1 和 PON3:功能相似但作用不同
副氧杂蒽醌酶 1(PON1)和副氧杂蒽醌酶 3(PON3)是位于高密度脂蛋白(HDL)表面的酶,具有类似的抗氧化特性,可能受到髓过氧化物酶(MPO)等其他蛋白质的调节,从而促使高密度脂蛋白从功能性转变为功能失调性。PON1 与阿尔茨海默病(AD)的关系已被广泛研究,但 PON3 的作用仍然未知。为了填补这一知识空白,该研究分析了99名阿尔茨海默病患者、100名轻度认知障碍(MCI)患者和79名认知正常对照组的PON3蛋白水平和PON1-芳香酯酶活性。结果显示,各组患者的血清 PON3 水平均保持不变。相反,与对照组相比,AD 和 MCI 患者的血清芳香族酯酶活性明显降低(两组比较的 p 均小于 0.001)。令人惊讶的是,丙烯酯酶活性与 MPO 蛋白浓度或活性之间没有相关性。然而,我们发现 PON3 与 MPO 浓度(r = 0.507,p < 0.0001)和 MPO 活性(r = 0.264,p < 0.01)均呈显著正相关。总之,我们首次证明了 PON1 和 PON3 与 AD 的不同关系,其中只有 PON1 的活性在这种疾病中有所下降,而 PON3 的水平保持不变。另一个值得注意的发现是 PON3 与 MPO 之间的选择性相关性,这可能表明 PON3 与高密度脂蛋白功能障碍有优先的物理关联。
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来源期刊
Antioxidants
Antioxidants Biochemistry, Genetics and Molecular Biology-Physiology
CiteScore
10.60
自引率
11.40%
发文量
2123
审稿时长
16.3 days
期刊介绍: Antioxidants (ISSN 2076-3921), provides an advanced forum for studies related to the science and technology of antioxidants. It publishes research papers, reviews and communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files and software regarding the full details of the calculation or experimental procedure, if unable to be published in a normal way, can be deposited as supplementary electronic material.
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