The importance of ether-phospholipids: A view from the perspective of mouse models

Silva, Tiago Ferreira da; Sousa, Vera; Malheiro, Ana Rita; Brites, Pedro

doi:10.1016/j.bbadis.2012.05.014

Cited by 77 publications

(65 citation statements)

References 106 publications

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“…For total ePC, there was a significant effect of the brain regions (F (2, 47) ϭ 41.8, PϽ0.01, Fig. 6) and an interaction between injury and the brain regions (F (2,31) ϭ30.6, PϽ0.01). For total ePE, there was a main effect of injury (F (1,38) ϭ5.9, Pϭ0.02), a main effect of brain regions (F (2,30) ϭ4.5, Pϭ0.02) and an interaction between them (F (2,30) ϭ18.1, PϽ0.01).…”

Section: Examination Of Epc and Epe Across Different Brain Regions Inmentioning

confidence: 95%

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: Examination Of Epc and Epe Across Different Brain Regions Inmentioning

confidence: 95%

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

et al. 2014

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“…The usage and characterization of several mouse models helped the understanding of RCDP pathogenesis, the characterization of mechanisms behind the disease, and the assessment of candidate treatments (Braverman et al 2010;Brites et al 2011;da Silva et al 2012). Studies using mouse models for RCDP demonstrated that plasmalogens are fundamental structural phospholipids and protect cells from damage caused by VLCFA accumulation (Brites et al 2009).…”

Section: The Role Of Plasmalogens and Fatty Alcohols In Diseasementioning

confidence: 99%

Plasmalogens and fatty alcohols in rhizomelic chondrodysplasia punctata and Sjögren‐Larsson syndrome

Malheiro¹,

Silva²,

Brites³

2014

J of Inher Metab Disea

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Plasmalogens are a special class of ether-phospholipids, best recognized by their vinyl-ether bond at the sn-1 position of the glycerobackbone and by the observation that their deficiency causes rhizomelic chondrodysplasia punctata (RCDP). The complex plasmalogen biosynthetic pathway involves multiple enzymatic steps carried-out in peroxisomes and in the endoplasmic reticulum. The rate limiting step in the biosynthesis of plasmalogens resides in the formation of the fatty alcohol responsible for the formation of an intermediate with an alkyl-linked moiety. The regulation in the biosynthesis of plasmalogens also takes place at this step using a feedback mechanism to stimulate or inhibit the biosynthesis. As such, fatty alcohols play a relevant role in the formation of ether-phospholipids. These advances in our understanding of complex lipid biosynthesis brought two seemingly distinct disorders into the spotlight. Sjögren-Larsson syndrome (SLS) is caused by defects in the microsomal fatty aldehyde dehydrogenase (FALDH) leading to the accumulation of fatty alcohols and fatty aldehydes. In RCDP cells, the defect in plasmalogens is thought to generate a feedback signal to increase their biosynthesis, through the activity of fatty acid reductases to produce fatty alcohols. However, the enzymatic defects in either glyceronephosphate O-acyltransferase (GNPAT) or alkylglycerone phosphate synthase (AGPS) disrupt the biosynthesis and result in the accumulation of the fatty alcohols. A detailed characterization on the processes and enzymes that govern these intricate biosynthetic pathways, as well as, the metabolic characterization of defects along the pathway should increase our understanding of the causes and mechanisms behind these disorders.

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“…Pex7 -/-mice display similar symptoms to those of patients with rhizomelic chondrodysplasia punctata and only 50 % survive the first 24 hours after birth. Although the exact cause of death has not been established, it has been attributed to the inability to feed due to reduced mobility (32,40). Brites et al reported that the Pex7 -/-mice display extremely reduced plasmalogen levels in almost all analysed tissues, including heart, and exhibit a reduced α-oxidation activity that results in the accumulation of phytanic acid in the plasma (32,40).…”

Section: Frontiers In Cardiovascular Researchmentioning

confidence: 99%

“…Although the exact cause of death has not been established, it has been attributed to the inability to feed due to reduced mobility (32,40). Brites et al reported that the Pex7 -/-mice display extremely reduced plasmalogen levels in almost all analysed tissues, including heart, and exhibit a reduced α-oxidation activity that results in the accumulation of phytanic acid in the plasma (32,40). Braverman et al, who analysed the phenotype of a hypomorphic Pex7 neo/neo mouse, reported a more than 10-fold increase in phytanic acid levels in the heart tissue of animals fed a phytol-containing diet (41,42).…”

Section: Frontiers In Cardiovascular Researchmentioning

confidence: 99%

Peroxisomes in cardiomyocytes and the peroxisome / peroxisome proliferator-activated receptor-loop

Colasante¹,

Chen²,

Ahlemeyer³

et al. 2015

Thromb Haemost

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SummaryIt is well established that the heart is strongly dependent on fatty acid metabolism. In cardiomyocytes there are two distinct sites for the β-oxidisation of fatty acids: the mitochondrion and the peroxisome. Although the metabolism of these two organelles is believed to be tightly coupled, the nature of this relationship has not been fully investigated. Recent research has established the significant contribution of mitochondrial function to cardiac ATP production under normal and pathological conditions. In contrast, limited information is available on peroxisomal function in the heart. This is despite these organelles harbouring metabolic pathways that are potentially cardioprotective, and findings that patients with peroxisomal diseases, such as adult Refsum´s disease, can develop heart failure. In this article, we provide a comprehensive overview on the current knowledge of peroxisomes and the regulation of lipid metabolism by PPARs in cardiomyocytes. We also present new experimental evidence on the differential expression of peroxisome-related genes in the heart chambers and demonstrate that even a mild peroxisomal biogenesis defect (Pex11α -/-) can induce profound alterations in the cardiomyocyte´s peroxisomal compartment and related gene expression, including the concomitant deregulation of specific PPARs. The possible impact of peroxisomal dysfunction in the heart is discussed and a model for the modulation of myocardial metabolism via a peroxisome/PPAR-loop is proposed.

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The importance of ether-phospholipids: A view from the perspective of mouse models

Cited by 77 publications

References 106 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

Plasmalogens and fatty alcohols in rhizomelic chondrodysplasia punctata and Sjögren‐Larsson syndrome

Peroxisomes in cardiomyocytes and the peroxisome / peroxisome proliferator-activated receptor-loop

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