Analysis of the mitochondrial proteome in multiple sclerosis cortex.
Analysis of the mitochondrial proteome in multiple sclerosis cortex.
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DOI：
10.1016/j.bbadis.2011.01.012
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发表时间：
2011-05
影响因子：
6.2
通讯作者：
McDonough, Jennifer
中科院分区：
文献类型：
--
作者：
Broadwater, Laurie;Pandit, Ashish;Clements, Robert;Azzam, Sausan;Vadnal, Jonathan;Sulak, Michael;Yong, V. Wee;Freeman, Ernest J.;Gregory, Roger B.;McDonough, Jennifer
线粒体功能障碍被认为在多发性硬化症(MS)的神经病理中起作用。此前，我们报道了MS核编码电子传输链基因转录的显著变化，并证实了复合体I和III组分的翻译变化导致其活性降低。为了更深入和有效地阐明线粒体及相关蛋白表达的潜在变化，我们利用表面增强激光解吸电离飞行时间质谱仪(SELDI-TOF-MS)对死后MS和对照大脑皮质的线粒体蛋白质组进行了表征。使用主成分分析(PCA)和层次聚类技术，我们能够分析SELDI-TOF光谱的差异模式，以揭示区分MS和对照样品的峰群。有四种蛋白质特别负责区分疾病和对照。多肽指纹图谱明确地识别了这些差异表达的蛋白质。已确定的与呼吸有关的三种蛋白质包括细胞色素C氧化酶亚基5b(COX5b)、脑组织特有的肌酸激酶同工酶和血红蛋白β链。第四种被鉴定的蛋白质是髓鞘碱性蛋白(MBP)。然后，我们研究了在实验性自身免疫性脑脊髓炎(EAE)小鼠模型中，这些变化是否一致。我们发现，MBP在EAE中也发生了类似的变化，但呼吸蛋白没有变化。这些数据表明，虽然EAE小鼠模型可能模拟了炎性脱髓鞘事件导致的MS神经病理的某些方面，但还有另一种不同的机制涉及MS灰质中的线粒体功能障碍，这在EAE中没有建模。
Mitochondrial dysfunction has been proposed to play a role in the neuropathology of multiple sclerosis (MS). Previously, we reported significant alterations in the transcription of nuclear-encoded electron transport chain genes in MS and confirmed translational alterations for components of Complexes I and III that resulted in reductions in their activity. To more thoroughly and efficiently elucidate potential alterations in the expression of mitochondrial and related proteins, we have characterized the mitochondrial proteome in postmortem MS and control cortex using Surface-Enhanced Laser Desorption Ionization Time of Flight Mass Spectrometry (SELDI-TOF-MS). Using principal component analysis (PCA) and hierarchical clustering techniques we were able to analyze the differential patterns of SELDI-TOF spectra to reveal clusters of peaks which distinguished MS from control samples. Four proteins in particular were responsible for distinguishing disease from control. Peptide fingerprint mapping unambiguously identified these differentially expressed proteins. Three proteins identified are involved in respiration including cytochrome c oxidase subunit 5b (COX5b), the brain specific isozyme of creatine kinase, and hemoglobin β-chain. The fourth protein identified was myelin basic protein (MBP). We then investigated whether these alterations were consistent in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. We found that MBP was similarly altered in EAE but the respiratory proteins were not. These data indicate that while the EAE mouse model may mimic aspects of MS neuropathology which result from inflammatory demyelinating events, there is another distinct mechanism involved in mitochondrial dysfunction in gray matter in MS which is not modeled in EAE.
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DOI：
10.1073/pnas.0813216106
发表时间：
2009-09-08
影响因子：
11.1
作者：
Biagioli, Marta;Pinto, Milena;Gustincich, Stefano
通讯作者：
Gustincich, Stefano
影响因子：
4.4
作者：
Bizzozero, O;DeJesus, G;Pastuszyn, A
通讯作者：
Pastuszyn, A
影响因子：
11.2
作者：
HATTORI, N;TANAKA, M;MIZUNO, Y
通讯作者：
MIZUNO, Y
影响因子：
11.2
作者：
Dutta, R;McDonough, J;Trapp, BD
通讯作者：
Trapp, BD
影响因子：
5.1
作者：
Chiasserini, D.;Di Filippo, M.;Sarchielli, P.
通讯作者：
Sarchielli, P.