Mass spectrometric studies on brain metabolism, using stable isotopes

Ando, Susumu; Tanaka, Yasukazu

doi:10.1002/mas.20045

Cited by 17 publications

(20 citation statements)

References 144 publications

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“…Essential FAs are transported to the BBB either as FFAs bound to albumin or carried with lipoproteins in esterified forms (i.e., PLs and triglycerides) that enter the endothelial cells through the luminal side and are liberated by lipoprotein lipases (65)(66)(67)(68)(69). It is suggested that a number of mechanisms on the abluminal side, such as a flip-flop mechanism and transporters that are specific for essential FA, particularly DHA, ultimately facilitate their entry into the brain (67,70).…”

Section: Discussionmentioning

confidence: 99%

Lipidomic analyses identify injury‐specific phospholipid changes 3 mo after traumatic brain injury

et al. 2014

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Phospholipid (PL) abnormalities are observed in the cerebrospinal fluid of patients with traumatic brain injury (TBI), suggesting their role in TBI pathology. Therefore, PL levels were examined in a TBI mouse model that received 1.8 mm deep controlled cortical impact injury or craniectomy only (control). The rotarod and Barnes maze acquisition and probe tests were performed within 2 wk after injury, with another probe test performed 3 mo postinjury. Liquid chromatography/mass spectrometry analyses were performed on lipid extracts from several brain regions and plasma from injured and control mice collected at 3 mo postinjury. Compared to controls, injured mice with sensorimotor and learning deficits had decreased levels of cortical and cerebellar phosphatidylcholine (PC) and phosphatidylethanolamine (PE) levels, while hippocampal PC, sphingomyelin and PE levels were elevated. Ether PE levels were lower in the cortices and plasma of injured animals. Polyunsaturated fatty acid-containing PC and PE species, particularly ratios of docosahexaenoic acid (DHA) to arachidonic acid, were lower in the hippocampi and cortices and plasma of injured mice. Given the importance of DHA in maintaining neuronal function and resolving inflammation and of peroxisomes in synthesis of ether PLs, normalizing these PLs may be a useful strategy for treating the chronic pathology of TBI.-Abdullah, L., Evans, J. E., Ferguson, S., Mouzon, B., Montague, H., Reed, J., Crynen, G., Emmerich, T., Crocker, M., Pelot, R., Mullan, M., Crawford, F. Lipidomic analyses identify injury-specific phospholipid changes 3 months after traumatic brain injury. FASEB J. 28, 5311-5321 (2014). www.fasebj.org Key Words: controlled cortical impact ⅐ mass spectrometry ⅐ phosphatidylcholine ⅐ phosphatidylethanolamine ⅐ phosphatidylinositol ⅐ sphingomyelin Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in the United States among adults from both the civilian and military populations. Due to the improvements made in military body armor and combat helmets over the past 2 decades, the rate of severe TBI associated with Iraq and Afghanistan deployments has decreased to 1% of the total TBI sustained by military personnel, a rate that is lower than those reported for previous deployments (1-3). Estimates from the U.S. Centers for Disease Control and Prevention suggest that severe TBI remains an important issue in the civilian population. In 2010, 2.5 million admissions to emergency departments were due to TBI (4) contributing to about a third of injury related deaths in the United States. The annual U.S. costs associated with TBI are estimated to be $75 billion, largely attributed to medical care, loss of productivity, and long-term disability (5). Although mild TBI occurs more frequently than severe TBI, the latter has the largest adverse effect on the activities of daily living of injured individuals and accounts for 90% of the total TBI-related medical costs (5). The primary injury is caused by the immediate force of the trauma a...

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Section: Discussionmentioning

confidence: 99%

Lipidomic analyses identify injury‐specific phospholipid changes 3 mo after traumatic brain injury

et al. 2014

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“…Metabolomic assessment provides a list of compounds that facilitates the estimation of metabolic flux through both single pathways and networks [41,42]. Metabolome analysis enables determination of abiotic conditions and genetic regulation of metabolic networks.…”

Section: Resultsmentioning

confidence: 99%

Metabolome searcher: a high throughput tool for metabolite identification and metabolic pathway mapping directly from mass spectrometry and using genome restriction

et al. 2015

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BackgroundMass spectrometric analysis of microbial metabolism provides a long list of possible compounds. Restricting the identification of the possible compounds to those produced by the specific organism would benefit the identification process. Currently, identification of mass spectrometry (MS) data is commonly done using empirically derived compound databases. Unfortunately, most databases contain relatively few compounds, leaving long lists of unidentified molecules. Incorporating genome-encoded metabolism enables MS output identification that may not be included in databases. Using an organism’s genome as a database restricts metabolite identification to only those compounds that the organism can produce.ResultsTo address the challenge of metabolomic analysis from MS data, a web-based application to directly search genome-constructed metabolic databases was developed. The user query returns a genome-restricted list of possible compound identifications along with the putative metabolic pathways based on the name, formula, SMILES structure, and the compound mass as defined by the user. Multiple queries can be done simultaneously by submitting a text file created by the user or obtained from the MS analysis software. The user can also provide parameters specific to the experiment’s MS analysis conditions, such as mass deviation, adducts, and detection mode during the query so as to provide additional levels of evidence to produce the tentative identification. The query results are provided as an HTML page and downloadable text file of possible compounds that are restricted to a specific genome. Hyperlinks provided in the HTML file connect the user to the curated metabolic databases housed in ProCyc, a Pathway Tools platform, as well as the KEGG Pathway database for visualization and metabolic pathway analysis.ConclusionsMetabolome Searcher, a web-based tool, facilitates putative compound identification of MS output based on genome-restricted metabolic capability. This enables researchers to rapidly extend the possible identifications of large data sets for metabolites that are not in compound databases. Putative compound names with their associated metabolic pathways from metabolomics data sets are returned to the user for additional biological interpretation and visualization. This novel approach enables compound identification by restricting the possible masses to those encoded in the genome.

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“…For more detailed and extended information on the important topic of stable isotope labeling methods in quantitative metabolite tracing, we would like to bring the recent reviews of Dettmer et al 120 and Ando and Tanaka, 121 to the readers' attention.…”

Section: Further Reading On Quantitative Techniques In Metabolite Tramentioning

confidence: 99%

Quantitative analysis with modern bioanalytical mass spectrometry and stable isotope labeling

Richards

Sojo

Keller

2007

Labelled Comp Radiopharmac

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The invention of new ionization techniques namely electrospray ionization and matrix-assisted laser desorption/ionization combined with the development of novel mass spectrometer analyzers and evolving isotope-ratio mass spectrometry have fueled the presence and use of modern mass spectrometric methodologies in many bioanalytical laboratories. Consequently, over the past two decades, a steadily increasing number of quantitative methods employing stable isotope labeling techniques have been reported, including prominent examples of methods to determine differential expression of proteins in disease studies, new-born screening for metabolic disorders, and tracing drugs or dietary compounds and their respective metabolites. Labeling biomolecules for quantitative studies using mass spectrometry has several challenges, including potentially insufficient labeling efficiency, ionization suppression, chromatographic separation of labeled and non-labeled compounds, and isotope exchange with the environment. It is not surprising that method development to minimize or eliminate existing limitations represents a very active and dynamic research area.

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Mass spectrometric studies on brain metabolism, using stable isotopes

Cited by 17 publications

References 144 publications

Lipidomic analyses identify injury‐specific phospholipid changes 3 mo after traumatic brain injury

Lipidomic analyses identify injury‐specific phospholipid changes 3 mo after traumatic brain injury

Metabolome searcher: a high throughput tool for metabolite identification and metabolic pathway mapping directly from mass spectrometry and using genome restriction

Quantitative analysis with modern bioanalytical mass spectrometry and stable isotope labeling

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