Myeloperoxidase and Advanced Oxidation Protein Products in the Cerebrospinal Fluid in Women and Men with Parkinson's Disease.

Myeloperoxidase and Advanced Oxidation Protein Products in the Cerebrospinal Fluid in Women and Men with Parkinson's Disease.
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DOI:
10.3390/antiox11061088
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发表时间:
2022-05-30
期刊:
Antioxidants (Basel, Switzerland)
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背景:髓过氧化物酶和高级氧化蛋白产物(一种髓过氧化物酶衍生的氯化加合物)与帕金森S病(PD)有关。人类MPO在帕金森病中也表现出基于性别的差异。目的:探讨男性和女性特发性帕金森病患者脑脊液中MPO和AOPP与运动特征的关系。方法:测定34例脑出血患者和30例正常对照组脑脊液和血清中MPO含量、活性和AOPP含量。测定脑脊液中白细胞和血脑屏障的完整性。分析MPO和AOPP与临床变量的相关性。结果:所有患者血脑屏障完整,脑脊液白细胞计数正常。脑脊液MPO的浓度和活性在患者和对照组中相似,但男性患者的脑脊液MPO含量显著高于女性患者(p=0.0084)。男性和女性患者脑脊液MPO浓度与病程相关(p<0.01)。与其余男性受试者相比,病程≥为12年的男性患者脑脊液中MPO浓度显著升高(p<0.01)。女性脑脊液MPO变化不明显。所有PD患者的血清MPO浓度和活性均显著高于对照组(P<0.0001)。脑脊液MPO与血清MPO无相关性。所有患者血清AOPP均可检出,但有53%的患者脑脊液AOPP未检出。AOPP在对照组中不能量化。结论:脑脊液MPO不是帕金森病的良好生物标志物,因为脑脊液MPO的平均浓度和活性在队列患者和对照组之间没有差别。男性和女性脑脊液MPO含量与病程呈正相关,但仅在病程大于12年的男性患者脑脊液MPO显著升高。可以推测,早期帕金森病患者的MPO相关免疫反应可能在所有患者中都较弱,但随后MPO相关免疫反应在男性而不是女性中逐渐增强。由于血脑屏障是完整的,而且脑脊液MPO与血清MPO无关,所以脑脊液髓过氧化物酶反映的是脑细胞中的MPO含量,而不是血源性细胞中的MPO含量。血清AOPP在所有患者中均可检测到,但未检测到对照组,这与PD患者血清中氯化应激的发生相一致。脑脊液中AOPP作为生物标志物的研究因其在脑脊液中的检出限而受到限制,无法对其进行评价。
Background: Myeloperoxidase (MPO) and advanced oxidation protein products, or AOPP (a type of MPO-derived chlorinated adducts), have been implicated in Parkinson´s disease (PD). Human MPO also show sex-based differences in PD. The objective was to study the relationship of MPO and AOPP in the cerebrospinal fluid (CSF) with motor features of idiopathic PD in male and female patients. Methods: MPO concentration and activity and AOPP content were measured in the CSF and serum in 34 patients and 30 controls. CSF leukocytes and the integrity of the blood-brain barrier were evaluated. Correlations of MPO and AOPP with clinical variables were examined. Results: The blood-brain barrier was intact and CSF leukocyte count was normal in all patients. CSF MPO concentration and activity were similar in the cohort of patients and controls, but CSF MPO content was significantly higher in male patients than in PD women (p = 0.0084). CSF MPO concentration correlated with disease duration in male and female patients (p < 0.01). CSF MPO concentration was significantly higher in men with disease duration ≥12 years versus the remainder of the male subjects (p < 0.01). Changes in CSF MPO in women were not significant. Serum MPO concentration and activity were significantly higher in all PD patients relative to controls (p < 0.0001). CSF MPO was not correlated with serum MPO. Serum AOPP were detected in all patients, but CSF AOPP was undetectable in 53% of patients. AOPP were not quantifiable in controls. Conclusions: CSF MPO is not a good biomarker for PD because mean CSF MPO concentration and activity are not different between the cohort of patients and controls. CSF MPO concentration positively correlated with disease duration in men and women, but CSF MPO is significantly enhanced only in male patients with disease duration longer than 12 years. It can be hypothesized that the MPO-related immune response in early-stage PD might be weak in all patients, but then the MPO-related immune response is progressively enhanced in men, not women. Since the blood-brain barrier is intact, and CSF MPO is not correlated with serum MPO, CSF myeloperoxidase would reflect MPO content in brain cells, not blood-derived cells. Finally, serum AOPP was detected in all patients, but not controls, which is consistent with the occurrence of chlorinative stress in blood serum in PD. The study of CSF AOPP as biomarker could not be assessed because the ELISA assay was hampered by its detection limit in the CSF.
DOI: 10.1016/j.neuro.2018.06.002
发表时间: 2018-07-01
期刊: NEUROTOXICOLOGY
影响因子: 3.4
作者:
Fernandez-Espejo, Emilio;Bis-Humbert, Cristian
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