A-to-I RNA editing is an important step in RNA processing in which specific adenosines in some RNA molecules are post-transcriptionally modified to inosines. RNA editing has emerged as a widespread mechanism for generating transcriptome diversity. However, there remain significant knowledge gaps about the variation and function of RNA editing. In order to determine the influence of genetic variation on A-to-I RNA editing, we integrate genomic and transcriptomic data from 445 human lymphoblastoid cell lines by combining an RNA editing QTL (edQTL) analysis with an allele-specific RNA editing (ASED) analysis. We identify 1054 RNA editing events associated with cis genetic polymorphisms. Additionally, we find that a subset of these polymorphisms is linked to genome-wide association study signals of complex traits or diseases. Finally, compared to random cis polymorphisms, polymorphisms associated with RNA editing variation are located closer spatially to their respective editing sites and have a more pronounced impact on RNA secondary structure. Our study reveals widespread cis variation in RNA editing among genetically distinct individuals and sheds light on possible phenotypic consequences of such variation on complex traits and diseases.

Wang E-S, Sun Y, Guo J-G, Gao X, Hu J-W, Zhou L, Hu J, Jiang C-C. Tetranectin and apolipoprotein A-I in cerebrospinal fluid as potential biomarkers for Parkinson’s disease.Acta Neurol Scand: 2010: 122: 350–359.© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objective – The application of biomarkers may potentially improve the efficiency of the diagnosis for Parkinson’s disease (PD). However, no reliable biomarker has been identified to date. This study is aimed to identify proteins that might serve as potential biomarkers for PD diagnosis or pathogenesis. Materials and methods – Two-dimensional difference gel electrophoresis (2D DIGE) technique, in combination with matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), was used to determine the differentially expressed cerebrospinal fluid (CSF) proteins in PD patients (n = 3) compared with normal controls (n = 3). Selected proteins were further confirmed by Western blotting analysis in the CSF of PD patients (n = 8), Alzheimer’s disease (AD) patients (n = 6) and normal control subjects (n = 7). Results – Eight proteins were identified after MS and protein database interrogation. In the CSF of PD patients, the expression levels of one isoform of apolipoprotein A-I (apoA-I), tetranectin, myosin phosphatase target subunit 1 (MYPT1), and two unknown proteins were down-regulated, whereas the expression levels of another apoA-I isoform, proapolipoprotein, and lipoprotein were up-regulated. Western blotting indicates that the expression of tetranectin was reduced in the CSF from PD patients and elevated in AD, while the expression of apoA-I was changed only in the CSF from PD patients. Conclusion – Our preliminary results suggest that tetranectin and apoA-I may serve as potential biomarkers for PD, though further validation is needed.

Aims: To investigate alterations in protein expression associated with deep brain stimulation (DBS) in an attempt to elucidate possible mechanisms of action. Methods: Cerebrospinal fluid (CSF), obtained from six Parkinson's disease (PD) patients (pre- and post-DBS) and from six normal healthy controls, was studied for differentially expressed proteins. 2-D DIGE, in combination with MALDI-TOF and TOF-TOF Mass Spectrometry (MS) or ESI-MS, was used to identify the changed proteins (3 PD patients and 3 controls). Selected proteins were further studied using western blotting (6 PD patients and 6 controls). Results: Twenty-one proteins were identified after MS and protein database interrogation. Apart from apolipoprotein A-I (apoA-I), the expression levels of complement C4 (C4), IgA, tetranectin, and extracellular superoxide dismutase (EC-SOD), detected by western blotting, correlated well with the 2-D DIGE results. In the follow-up period, the expression levels of C4, apoA-I and IgA were stable whereas EC-SOD and tetranectin were significantly elevated. In addition, when DBS was ceased in one patient due to a suicide attempt, the levels of EC-SOD and tetranectin significantly decreased. Conclusion: Our preliminary results suggest that variations in the expression levels of EC-SOD and tetranectin in CSF is related to DBS.

General anesthesia is a powerful and indispensable tool to ensure the accomplishment of surgical procedures or clinical examinations. Sevoflurane as an inhalational anesthetic without unpleasant odor is commonly used in clinical practice, especially for pediatric surgery. However, the toxicity caused by sevoflurane has gained growing attention. Mitochondria play a key role in maintaining cellular metabolism and survival. To maintain the stability of mitochondrial homeostasis, they are constantly going through fusion and fission. Also, damaged mitochondria need to be degraded by autophagy, termed as mitophagy. Accumulating evidence proves that sevoflurane exposure in young age could lead to cell toxicity by triggering the mitochondrial pathway of apoptosis, inducing the abnormalities of mitochondrial dynamics and mitophagy. In the present review, we focus on the current understanding of mitochondrial apoptosis, dynamics and mitophagy in cell function, the implications for cell toxicity in response to sevoflurane, and their underlying potential mechanisms.