Erythrocyte Phospholipid and Polyunsaturated Fatty Acid Composition in Diabetic Retinopathy

Koehrer, Philippe; Saab, Sarah; Berdeaux, Olivier; Isaico, Rodica; Grégoire, Stéphane; Cabaret, Stéphanie; Bron, Alain M.; Creuzot‐Garcher, Catherine; Brétillon, Lionel; Acar, Niyazi

doi:10.1371/journal.pone.0106912

Cited by 53 publications

(48 citation statements)

References 38 publications

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“…4-Hydroxyalkenals are the most toxic products in lipid peroxidation and were found in the retina as early as 6 weeks of diabetes 75 . Our results was found to be in agreement with several studies on diabetes-induced changes in retinal fatty acid metabolism 76,77 that revealed a significant decrease in unsaturation level in diabetic retina. Lipid peroxidation serves as an indicator of the oxidative stress in diabetes mellitus 52 , and it occurs due to the abundance of unsaturated fatty acids in biological membranes that are mainly attacked by free radicals.…”

Section: Discussionsupporting

confidence: 93%

Retinal oxidative stress at the onset of diabetes determined by synchrotron FTIR widefield imaging: towards diabetes pathogenesis

Aboualizadeh

Ranji

Sorenson

et al. 2017

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Diabetic retinopathy is a microvascular complication of diabetes that can lead to blindness. In the present study, we aimed to determine the nature of diabetes-induced, highly localized biochemical changes in the neuroretina at the onset of diabetes. High-resolution synchrotron Fourier transform infrared (s-FTIR) wide field microscopy coupled with multivariate analysis (PCA-LDA) was employed to identify biomarkers of diabetic retinopathy with spatial resolution at the cellular level. We compared retinal tissue prepared from 6-week-old Ins2Akita/+ heterozygous (Akita/+, N=6; a model of diabetes) male mice compared with the wild-type (control, N=6) mice. Male Akita/+ mice become diabetic at 4-weeks of age. Significant differences (P<0.001) in the presence of biomarkers associated with diabetes and segregation of spectra was achieved. Differentiating IR bands attributed to nucleic acids (964, 1051, 1087, 1226 and 1710 cm−1), proteins (1662, 1608 cm−1) and fatty acids (2854, 2923, 2956 and 3012 cm−1) were observed between the Akita/+ and the WT samples. Comparison between distinctive layers of the retina, namely the photoreceptor retinal layer (PRL), outer plexiform layer (OPL), inner nuclear layer (INL) and inner plexiform layer (IPL) suggested that the photoreceptor layer is the most susceptible layer to the oxidative stress in short-term diabetes. Spatially-resolved chemical images indicated heterogeneities and oxidative-stress induced alterations in the diabetic retina tissue morphology compared with WT retina. In this study, the spectral biomarkers and the spatial biochemical alterations in the diabetic retina and in specific layers were identified for the first time. We believe that the conclusions drawn from these studies will help to bridge the gap in our understanding of the molecular and cellular mechanism that contribute to pathobiology of diabetic retinopathy.

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Section: Discussionsupporting

confidence: 93%

Retinal oxidative stress at the onset of diabetes determined by synchrotron FTIR widefield imaging: towards diabetes pathogenesis

Aboualizadeh

Ranji

Sorenson

et al. 2017

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“…Although farE is induced by and promotes resistance to linoleic acid, S. aureus would be exposed to a changing diversity and abundance of free fatty acids, dependent on the context within the human body. In a tissue abscess, pus contains high concentrations of unsaturated free fatty acids (UFFA), which could be derived from triglyceride (18,51) or human cell membrane phospholipid, where each of the major unsaturated fatty acids, oleic (C 18:1 ), linoleic (C 18:2 ), and arachidonic (C 20:4 ) acid, comprises approximately 13 to 15% of the total fatty acid content (22,23). Conversely, although sapienic acid or its isomer palmitoleic acid (C 16:1 ) do not comprise a major proportion of the fatty acid profile of phospholipid, sapienic acid is the major unsaturated fatty acid in human sebum, both as free fatty acid and in sebum triglyceride (14,52).…”

Section: Resultsmentioning

confidence: 99%

“…In other work, bactericidal assays conducted with human nasal secretions established that cholesterol esters of linoleic and arachidonic acids were the principal components with bactericidal activity toward Pseudomonas aeruginosa, which does not colonize the nose, but that they did not affect viability of S. aureus (16); linoleic acid is also the principal antimicrobial fatty acid in homogenates of murine tissue abscesses (18,51). Although arachidonic acid was not identified as a major fatty acid in abscess homogenates, it is a major unsaturated fatty acid in erythrocyte and leukocyte membrane phospholipid (23,70), from which it is released by phospholipases at sites of infection and rapidly converted to inflammatory mediators (71). Therefore, the induction of farE in response to linoleic and arachidonic acids may represent an evolutionary feature that contributes to the success of S. aureus as a human pathogen.…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, linoleic acid is an essential fatty acid for humans, which must be obtained from dietary sources, and is an essential precursor for synthesis of arachidonic acid. These two unsaturated fatty acids comprise a major proportion of unsaturated fatty acids in membrane phospholipid (22,23). Therefore, the ability to sense and respond to linoleic acid could represent a specific sensory mechanism to signal colonization or infection of a human host, and yet specific mechanisms for regulating gene expression and intrinsic resistance in response to linoleic acid have not been reported.…”

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confidence: 99%

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Inducible Expression of a Resistance-Nodulation-Division-Type Efflux Pump in Staphylococcus aureus Provides Resistance to Linoleic and Arachidonic Acids

et al. 2015

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Although Staphylococcus aureus is exposed to antimicrobial fatty acids on the skin, in nasal secretions, and in abscesses, a specific mechanism of inducible resistance to this important facet of innate immunity has not been identified. Here, we have sequenced the genome of S. aureus USA300 variants selected for their ability to grow at an elevated concentration of linoleic acid. The fatty acid-resistant clone FAR7 had a single nucleotide polymorphism resulting in an H 121 Y substitution in an uncharacterized transcriptional regulator belonging to the AcrR family, which was divergently transcribed from a gene encoding a member of the resistance-nodulation-division superfamily of multidrug efflux pumps. We named these genes farR and farE, for regulator and effector of fatty acid resistance, respectively. Several lines of evidence indicated that FarE promotes efflux of antimicrobial fatty acids and is regulated by FarR. First, expression of farE was strongly induced by arachidonic and linoleic acids in an farRdependent manner. Second, an H 121 Y substitution in FarR resulted in increased expression of farE and was alone sufficient to promote increased resistance of S. aureus to linoleic acid. Third, inactivation of farE resulted in a significant reduction in the inducible resistance of S. aureus to the bactericidal activity of 100 M linoleic acid, increased accumulation of [ 14 C]linoleic acid by growing cells, and severely impaired growth in the presence of nonbactericidal concentrations of linoleic acid. Cumulatively, these findings represent the first description of a specific mechanism of inducible resistance to antimicrobial fatty acids in a Gram-positive pathogen. IMPORTANCEStaphylococcus aureus colonizes approximately 25% of humans and is a leading cause of human infectious morbidity and mortality. To persist on human hosts, S. aureus must have intrinsic defense mechanisms to cope with antimicrobial fatty acids, which comprise an important component of human innate defense mechanisms. We have identified a novel pair of genes, farR and farE, that constitute a dedicated regulator and effector of S. aureus resistance to linoleic and arachidonic acids, which are major fatty acids in human membrane phospholipid. Expression of farE, which encodes an efflux pump, is induced in an farRdependent mechanism, in response to these antimicrobial fatty acids that would be encountered in a tissue abscess. Staphylococcus aureus has a dichotomous relation with human hosts, being able to establish an asymptomatic commensal relationship, but is also historically known as a leading cause of human infectious morbidity and mortality. Significantly, death attributed to S. aureus in the United States is now comparable to mortality rates for AIDS, tuberculosis, and viral hepatitis (1-3). Not surprisingly, therefore, S. aureus has been the subject of intensive research on mechanisms of pathogenesis and acquisition and transfer of antibiotic resistance and of efforts to identify potential vaccine antigens (4-6). Until the late ...

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“…Direct trans-esterification of lipids can either be acid or base-catalyzed. Reagents commonly used for acid catalyzed trans-esterification are: methanolic hydrochloric and sulfuric acid [33]; and boron trifluoride in methanol [10,34,35] whereas reagents that have been used for base-catalyzed trans-esterification of biological samples are sodium methoxide [16,31] and potassium hydroxide in methanol [6]. Boron trifluoride in methanol (12-14%) is the most often used for transesterification of RBC lipids [26].…”

Section: Methylation Proceduresmentioning

confidence: 99%

A Rapid and Simple Method for Fatty Acid Profiling and Determination of ω-3 Index in Red Blood Cells

Akinyemi¹,

Bruckner²,

Johnson³

et al. 2017

TONUTRJ

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Fatty acid profiling has become a very useful and effective tool in the diagnosis, prevention and treatment of several diseases with cardiovascular disease being particularly important. In order to arrive at accurate conclusions that would help promote the health of individuals plagued by such diseases, not only excellent laboratory methods are required, but also very important monitoring responses to treatment. Improvements in methods of fatty acid profiling in biological systems regarding safety of extraction, precision and time for analysis are valuable. The ω-3 index (a measure of the amount of eicosapentaenoic acid, EPA, and docosahexaenoic acid, DHA, in Red Blood Cell membranes expressed as the percent of total fatty acids) is of growing interest because it has been reported to provide prognostic information regarding the risk for heart diseases. Sodium methoxide has been widely used for the determination of ω -3 fatty acids in food samples. This study demonstrates that sodium methoxide can be used effectively in RBC fatty acid profiling and determination of the ω-3 index. Briefly, the fatty acid profiles and ω-3 index of red blood cell samples were analyzed and results compared using three different methods: a two-step extraction and methylation method described by Hara and Radin, a single step extraction and methylation method described by Harris et al. and the sodium methoxide method.Our results revealed that there were no statistically significant differences (p<0.05) between the three methods for the representative fatty acids, [16:0 (p = 0.10), 18:0 (p=0.40), 18:1(ω9) (p = 0.29), 18:2(ω6) (p = 0.95), 18:3(ω3) (p = 0.50), 20:5(ω3) (p=0.56), 22:6(ω3) (p = 0.06)] and ω-3 index (p = 0.11) except for 20:4(ω6), (P = 0.02). In conclusion, we show that sodium methoxide can be used effectively in a one-step extraction and methylation procedure for high throughput analysis of fatty acids in red blood cell membranes. It is rapid (10 minute extraction and methylation), simple, safer than and as accurate as other commonly reported methods.

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Erythrocyte Phospholipid and Polyunsaturated Fatty Acid Composition in Diabetic Retinopathy

Cited by 53 publications

References 38 publications

Retinal oxidative stress at the onset of diabetes determined by synchrotron FTIR widefield imaging: towards diabetes pathogenesis

Retinal oxidative stress at the onset of diabetes determined by synchrotron FTIR widefield imaging: towards diabetes pathogenesis

Inducible Expression of a Resistance-Nodulation-Division-Type Efflux Pump in Staphylococcus aureus Provides Resistance to Linoleic and Arachidonic Acids

A Rapid and Simple Method for Fatty Acid Profiling and Determination of ω-3 Index in Red Blood Cells

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