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Article ; Online: The wide world of non-mammalian phospholipase D enzymes.

Wang, Y / Wakelam, M J O / Bankaitis, V A / McDermott, M I

2023 Volume 91, Page(s) 101000

Abstract: Phospholipase D (PLD) hydrolyses phosphatidylcholine (PtdCho) to produce free choline and the critically important lipid signaling molecule phosphatidic acid (PtdOH). Since the initial discovery of PLD activities in plants and bacteria, PLDs have been ... ...

Abstract	Phospholipase D (PLD) hydrolyses phosphatidylcholine (PtdCho) to produce free choline and the critically important lipid signaling molecule phosphatidic acid (PtdOH). Since the initial discovery of PLD activities in plants and bacteria, PLDs have been identified in a diverse range of organisms spanning the taxa. While widespread interest in these proteins grew following the discovery of mammalian isoforms, research into the PLDs of non-mammalian organisms has revealed a fascinating array of functions ranging from roles in microbial pathogenesis, to the stress responses of plants and the developmental patterning of flies. Furthermore, studies in non-mammalian model systems have aided our understanding of the entire PLD superfamily, with translational relevance to human biology and health. Increasingly, the promise for utilization of non-mammalian PLDs in biotechnology is also being recognized, with widespread potential applications ranging from roles in lipid synthesis, to their exploitation for agricultural and pharmaceutical applications.
MeSH term(s)	Humans ; Animals ; Phospholipase D/genetics ; Phospholipase D/metabolism ; Plants ; Signal Transduction ; Phosphatidic Acids/metabolism ; Choline ; Mammals/metabolism
Chemical Substances	Phospholipase D (EC 3.1.4.4) ; Phosphatidic Acids ; Choline (N91BDP6H0X)
Language	English
Publishing date	2023-12-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2667413-0
ISSN	2212-4934 ; 2212-4926
ISSN (online)	2212-4934
ISSN	2212-4926
DOI	10.1016/j.jbior.2023.101000
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Article ; Online: Mammalian phospholipase D: Function, and therapeutics.

McDermott, M I / Wang, Y / Wakelam, M J O / Bankaitis, V A

Progress in lipid research

2019 Volume 78, Page(s) 101018

Abstract: Despite being discovered over 60 years ago, the precise role of phospholipase D (PLD) is still being elucidated. PLD enzymes catalyze the hydrolysis of the phosphodiester bond of glycerophospholipids producing phosphatidic acid and the free headgroup. ... ...

Abstract	Despite being discovered over 60 years ago, the precise role of phospholipase D (PLD) is still being elucidated. PLD enzymes catalyze the hydrolysis of the phosphodiester bond of glycerophospholipids producing phosphatidic acid and the free headgroup. PLD family members are found in organisms ranging from viruses, and bacteria to plants, and mammals. They display a range of substrate specificities, are regulated by a diverse range of molecules, and have been implicated in a broad range of cellular processes including receptor signaling, cytoskeletal regulation and membrane trafficking. Recent technological advances including: the development of PLD knockout mice, isoform-specific antibodies, and specific inhibitors are finally permitting a thorough analysis of the in vivo role of mammalian PLDs. These studies are facilitating increased recognition of PLD's role in disease states including cancers and Alzheimer's disease, offering potential as a target for therapeutic intervention.
MeSH term(s)	Alzheimer Disease/drug therapy ; Alzheimer Disease/metabolism ; Animals ; Humans ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Phospholipase D/antagonists & inhibitors ; Phospholipase D/deficiency ; Phospholipase D/metabolism
Chemical Substances	Phospholipase D (EC 3.1.4.4)
Language	English
Publishing date	2019-12-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	282560-0
ISSN	1873-2194 ; 0079-6832 ; 0163-7827
ISSN (online)	1873-2194
ISSN	0079-6832 ; 0163-7827
DOI	10.1016/j.plipres.2019.101018
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Article ; Online: The Effect of a

Kochaj, Rafael M / Martelletti, Elisa / Ingham, Neil J / Buniello, Annalisa / Sousa, Bebiana C / Wakelam, Michael J O / Lopez-Clavijo, Andrea F / Steel, Karen P

Cells

2022 Volume 11, Issue 20

Abstract: Peroxisome biogenesis disorders (due ... ...

Abstract	Peroxisome biogenesis disorders (due to
MeSH term(s)	Animals ; Child, Preschool ; Humans ; Mice ; Ear, Inner/metabolism ; Hearing/physiology ; Hearing Loss/genetics ; Hearing Loss/metabolism ; Lipoproteins/metabolism ; Membrane Proteins/metabolism ; Mutation/genetics ; Peroxins/genetics ; Plasmalogens
Chemical Substances	Lipoproteins ; Membrane Proteins ; Peroxins ; Pex3 protein, human ; Plasmalogens ; PEX3 protein, mouse
Language	English
Publishing date	2022-10-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11203206
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Article ; Online: Extracellular vesicles: lipids as key components of their biogenesis and functions.

Record, Michel / Silvente-Poirot, Sandrine / Poirot, Marc / Wakelam, Michael J O

Journal of lipid research

2018 Volume 59, Issue 8, Page(s) 1316–1324

Abstract: Intercellular communication has been known for decades to involve either direct contact between cells or to operate via circulating molecules, such as cytokines, growth factors, or lipid mediators. During the last decade, we have begun to appreciate the ... ...

Abstract	Intercellular communication has been known for decades to involve either direct contact between cells or to operate via circulating molecules, such as cytokines, growth factors, or lipid mediators. During the last decade, we have begun to appreciate the increasing importance of intercellular communication mediated by extracellular vesicles released by viable cells either from plasma membrane shedding (microvesicles, also named microparticles) or from an intracellular compartment (exosomes). Exosomes and microvesicles circulate in all biological fluids and can trigger biological responses at a distance. Their effects include a large variety of biological processes, such as immune surveillance, modification of tumor microenvironment, or regulation of inflammation. Extracellular vesicles can carry a large array of active molecules, including lipid mediators, such as eicosanoids, proteins, and nucleic acids, able to modify the phenotype of receiving cells. This review will highlight the role of the various lipidic pathways involved in the biogenesis and functions of microvesicles and exosomes.
MeSH term(s)	Cell-Derived Microparticles/metabolism ; Exosomes/metabolism ; Extracellular Vesicles/metabolism ; Humans ; Lipid Metabolism ; Signal Transduction
Language	English
Publishing date	2018-05-15
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	80154-9
ISSN	1539-7262 ; 0022-2275
ISSN (online)	1539-7262
ISSN	0022-2275
DOI	10.1194/jlr.E086173
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Article ; Online: A Multicenter Validity Study of Four Smartphone Hearing Test Apps in Optimized and Home Environments.

The Laryngoscope

2024

Abstract: Objective: Pure tone audiometry (PTA) is the gold standard for hearing assessment. However, it requires access to specialized equipment. Smartphone audiometry applications (apps) have been developed to perform automated threshold audiometry and could ... ...

Abstract	Objective: Pure tone audiometry (PTA) is the gold standard for hearing assessment. However, it requires access to specialized equipment. Smartphone audiometry applications (apps) have been developed to perform automated threshold audiometry and could allow patients to perform self-administered screening or monitoring. This study aimed to assess the validity and feasibility of patients using apps to self-assess hearing thresholds at home, with comparison to PTA. Methods: A multi-center, prospective randomized study was conducted amongst patients undergoing PTA in clinics. Participants were randomly allocated to one of four publicly-available apps designed to measure pure tone thresholds. Participants used an app once in optimal sound-treated conditions and a further three times at home. Ear-specific frequency-specific thresholds and pure tone average were compared using Pearson correlation coefficient. The percentage of app hearing tests with results within ±10 dB of PTA was calculated. Patient acceptability was assessed via an online survey. Results: One hundred thirty-nine participants submitted data. The results of two at-home automated smartphone apps correlated strongly/very strongly with PTA average and their frequency-specific median was within ±10 dB accuracy. Smartphone audiometry performed in sound-treated and home conditions were very strongly correlated. The apps were rated as easy/very easy to use by 90% of participants and 90% would be happy/very happy to use an app to monitor their hearing. Conclusion: Judicious use of self-performed smartphone audiometry was both valid and feasible for two of four apps. It could provide frequency-specific threshold estimates at home, potentially allowing assessments of patients remotely or monitoring of fluctuating hearing loss. Level of evidence: 2 Laryngoscope, 2024.
Language	English
Publishing date	2024-01-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	80180-x
ISSN	1531-4995 ; 0023-852X
ISSN (online)	1531-4995
ISSN	0023-852X
DOI	10.1002/lary.31256
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Article ; Online: Integrated lipidomics and proteomics reveal cardiolipin alterations, upregulation of HADHA and long chain fatty acids in pancreatic cancer stem cells.

Di Carlo, Claudia / Sousa, Bebiana C / Manfredi, Marcello / Brandi, Jessica / Dalla Pozza, Elisa / Marengo, Emilio / Palmieri, Marta / Dando, Ilaria / Wakelam, Michael J O / Lopez-Clavijo, Andrea F / Cecconi, Daniela

Scientific reports

2021 Volume 11, Issue 1, Page(s) 13297

Abstract: Pancreatic cancer stem cells (PCSCs) play a key role in the aggressiveness of pancreatic ductal adenocarcinomas (PDAC); however, little is known about their signaling and metabolic pathways. Here we show that PCSCs have specific and common proteome and ... ...

Abstract	Pancreatic cancer stem cells (PCSCs) play a key role in the aggressiveness of pancreatic ductal adenocarcinomas (PDAC); however, little is known about their signaling and metabolic pathways. Here we show that PCSCs have specific and common proteome and lipidome modulations. PCSCs displayed downregulation of lactate dehydrogenase A chain, and upregulation of trifunctional enzyme subunit alpha. The upregulated proteins of PCSCs are mainly involved in fatty acid (FA) elongation and biosynthesis of unsaturated FAs. Accordingly, lipidomics reveals an increase in long and very long-chain unsaturated FAs, which are products of fatty acid elongase-5 predicted as a key gene. Moreover, lipidomics showed the induction in PCSCs of molecular species of cardiolipin with mixed incorporation of 16:0, 18:1, and 18:2 acyl chains. Our data indicate a crucial role of FA elongation and alteration in cardiolipin acyl chain composition in PCSCs, representing attractive therapeutic targets in PDAC.
MeSH term(s)	Carcinoma, Pancreatic Ductal/metabolism ; Cardiolipins/metabolism ; Humans ; Lipid Metabolism ; Lipidomics ; Mitochondrial Trifunctional Protein, alpha Subunit/metabolism ; Neoplastic Stem Cells/metabolism ; Pancreatic Neoplasms/metabolism ; Proteomics ; Up-Regulation
Chemical Substances	Cardiolipins ; HADHA protein, human (EC 1.1.1.211) ; Mitochondrial Trifunctional Protein, alpha Subunit (EC 1.1.1.211)
Language	English
Publishing date	2021-06-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-92752-5
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Article: Identification of a Thyroid Hormone Derivative as a Pleiotropic Agent for the Treatment of Alzheimer's Disease.

Runfola, Massimiliano / Perni, Michele / Yang, Xiaoting / Marchese, Maria / Bacci, Andrea / Mero, Serena / Santorelli, Filippo M / Polini, Beatrice / Chiellini, Grazia / Giuliani, Daniela / Vilella, Antonietta / Bodria, Martina / Daini, Eleonora / Vandini, Eleonora / Rudge, Simon / Gul, Sheraz / Wakelam, Michale O J / Vendruscolo, Michele / Rapposelli, Simona

Pharmaceuticals (Basel, Switzerland)

2021 Volume 14, Issue 12

Abstract: The identification of effective pharmacological tools for Alzheimer's disease (AD) represents one of the main challenges for therapeutic discovery. Due to the variety of pathological processes associated with AD, a promising route for pharmacological ... ...

Abstract	The identification of effective pharmacological tools for Alzheimer's disease (AD) represents one of the main challenges for therapeutic discovery. Due to the variety of pathological processes associated with AD, a promising route for pharmacological intervention involves the development of new chemical entities that can restore cellular homeostasis. To investigate this strategy, we designed and synthetized SG2, a compound related to the thyroid hormone thyroxine, that shares a pleiotropic activity with its endogenous parent compound, including autophagic flux promotion, neuroprotection, and metabolic reprogramming. We demonstrate herein that SG2 acts in a pleiotropic manner to induce recovery in a
Language	English
Publishing date	2021-12-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph14121330
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Article ; Online: BioPAN: a web-based tool to explore mammalian lipidome metabolic pathways on LIPID MAPS.

Gaud, Caroline / C Sousa, Bebiana / Nguyen, An / Fedorova, Maria / Ni, Zhixu / O'Donnell, Valerie B / Wakelam, Michael J O / Andrews, Simon / Lopez-Clavijo, Andrea F

F1000Research

2021 Volume 10, Page(s) 4

Abstract: Lipidomics increasingly describes the quantification using mass spectrometry of all lipids present in a biological sample. As the power of lipidomics protocols increase, thousands of lipid molecular species from multiple categories can now be profiled ... ...

Abstract	Lipidomics increasingly describes the quantification using mass spectrometry of all lipids present in a biological sample. As the power of lipidomics protocols increase, thousands of lipid molecular species from multiple categories can now be profiled in a single experiment. Observed changes due to biological differences often encompass large numbers of structurally-related lipids, with these being regulated by enzymes from well-known metabolic pathways. As lipidomics datasets increase in complexity, the interpretation of their results becomes more challenging. BioPAN addresses this by enabling the researcher to visualise quantitative lipidomics data in the context of known biosynthetic pathways. BioPAN provides a list of genes, which could be involved in the activation or suppression of enzymes catalysing lipid metabolism in mammalian tissues.
Language	English
Publishing date	2021-01-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2699932-8
ISSN	2046-1402 ; 2046-1402
ISSN (online)	2046-1402
ISSN	2046-1402
DOI	10.12688/f1000research.28022.2
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Article: Diacylglycerol--when is it an intracellular messenger?

Wakelam, M J

Biochimica et biophysica acta

1998 Volume 1436, Issue 1-2, Page(s) 117–126

Abstract: Distinct, structurally different forms of sn-1,2-diacylglycerol are found in cells, these are polyunsaturated, mono- or di-unsaturated and saturated. The pathways that generate or metabolise sn-1, 2-diacylglycerol are reviewed. The evidence that it is ... ...

Abstract	Distinct, structurally different forms of sn-1,2-diacylglycerol are found in cells, these are polyunsaturated, mono- or di-unsaturated and saturated. The pathways that generate or metabolise sn-1, 2-diacylglycerol are reviewed. The evidence that it is the polyunsaturated forms of sn-1,2-diacylglycerol, but the more saturated forms of phosphatidate which function as intracellular signals is considered.
MeSH term(s)	Animals ; Diglycerides/biosynthesis ; Diglycerides/chemistry ; Diglycerides/physiology ; Phosphatidic Acids/metabolism ; Phospholipase D/metabolism ; Signal Transduction ; Structure-Activity Relationship
Chemical Substances	Diglycerides ; Phosphatidic Acids ; Phospholipase D (EC 3.1.4.4)
Language	English
Publishing date	1998-09-15
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/s0005-2760(98)00123-4
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Article: Abundances of sulphur molecules in the Horsehead nebula First NS

Rivière-Marichalar, P / Fuente, A / Goicoechea, J R / Pety, J / Le Gal, R / Gratier, P / Guzmán, V / Roueff, E / Loison, J C / Wakelam, V / Gerin, M

Astronomy and astrophysics

2019 Volume 628

Abstract: Context: Sulphur is one of the most abundant elements in the Universe (S/H: Aims: Our goal is to complete the inventory of S-bearing molecules and their abundances in the prototypical photodissociation region (PDR) the Horsehead nebula to gain ... ...

Abstract	Context: Sulphur is one of the most abundant elements in the Universe (S/H Aims: Our goal is to complete the inventory of S-bearing molecules and their abundances in the prototypical photodissociation region (PDR) the Horsehead nebula to gain insight into sulphur chemistry in UV irradiated regions. Based on the WHISPER (Wide-band High-resolution Iram-30m Surveys at two positions with Emir Receivers) millimeter (mm) line survey, our goal is to provide an improved and more accurate description of sulphur species and their abundances towards the core and PDR positions in the Horsehead. Methods: The Monte Carlo Markov Chain (MCMC) methodology and the molecular excitation and radiative transfer code RADEX were used to explore the parameter space and determine physical conditions and beam-averaged molecular abundances. Results: A total of 13 S-bearing species (CS, SO, SO Conclusions: This is the first complete study of S-bearing species towards a PDR. Our study shows that CS, SO, and H
Language	English
Publishing date	2019-07-29
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1458466-9
ISSN	1432-0746 ; 0004-6361
ISSN (online)	1432-0746
ISSN	0004-6361
DOI	10.1051/0004-6361/201935354
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