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Nicolas G. Bazan - One of the best experts on this subject based on the ideXlab platform.
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Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection.
Molecular aspects of medicine, 2018Co-Authors: Nicolas G. BazanAbstract:The functional significance of the selective enrichment of the omega-3 essential fatty acid docosahexaenoic acid (DHA; 22C and 6 double bonds) in cellular membrane phospholipids of the nervous system is being clarified by defining its specific roles on membrane protein function and by the uncovering of the bioactive mediators, Docosanoids and elovanoids (ELVs). Here, we describe the preferential uptake and DHA metabolism in photoreceptors and brain as well as the significance of the Adiponectin receptor 1 in DHA retention and photoreceptor cell (PRC) survival. We now know that this integral membrane protein is engaged in DHA retention as a necessary event for the function of PRCs and retinal pigment epithelial (RPE) cells. We present an overview of how a) NPD1 selectively mediates preconditioning rescue of RPE and PR cells; b) NPD1 restores aberrant neuronal networks in experimental epileptogenesis; c) the decreased ability to biosynthesize NPD1 in memory hippocampal areas of early stages of Alzheimer's disease takes place; d) NPD1 protection of dopaminergic circuits in an in vitro model using neurotoxins; and e) bioactivity elicited by DHA and NPD1 activate a neuroprotective gene-expression program that includes the expression of Bcl-2 family members affected by Aβ42, DHA, or NPD1. In addition, we highlight ELOVL4 (ELOngation of Very Long chain fatty acids-4), specifically the neurological and ophthalmological consequences of its mutations, and their role in providing precursors for the biosynthesis of ELVs. Then we outline evidence of ELVs ability to protect RPE cells, which sustain PRC integrity. In the last section, we present a summary of the protective bioactivity of Docosanoids and ELVs in experimental ischemic stroke. The identification of early mechanisms of neural cell survival mediated by DHA-synthesized ELVs and Docosanoids contributes to the understanding of cell function, pro-homeostatic cellular modulation, inflammatory responses, and innate immunity, opening avenues for prevention and therapeutic applications in neurotrauma, stroke and neurodegenerative diseases.
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Retinal Pigment Epithelium and Photoreceptor Preconditioning Protection Requires Docosanoid Signaling
Cellular and Molecular Neurobiology, 2018Co-Authors: Eric J. Knott, William C Gordon, Khanh Do, Nicolas G. BazanAbstract:Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are necessary for functional cell integrity. Preconditioning (PC), as we define it, is an acquired protection or resilience by a cell, tissue, or organ to a lethal stimulus enabled by a previous sublethal stressor or stimulus. In this study, we provide evidence that the omega-3 fatty acid docosahexaenoic acid (DHA) and its derivatives, the Docosanoids 17-hydroxy docosahexaenoic acid (17-HDHA) and neuroprotectin D1 (NPD1), facilitate cell survival in both in vitro and in vivo models of retinal PC. We also demonstrate that PC requires the enzyme 15-lipoxygenase-1 (15-LOX-1), which synthesizes 17-HDHA and NPD1, and that this is specific to Docosanoid signaling despite the concomitant release of the omega-6 arachidonic acid and eicosanoid synthesis. These findings advocate that DHA and Docosanoids are protective enablers of PC in photoreceptor and retinal pigment epithelial cells.
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elovanoids are novel cell specific lipid mediators necessary for neuroprotective signaling for photoreceptor cell integrity
Scientific Reports, 2017Co-Authors: Bokkyoo Jun, Rong Yang, William C Gordon, Pranab K Mukherjee, Aram Asatryan, Marieaudrey Ines Kautzmann, Jessica Heap, Surjyadipta Bhattacharjee, Nicos A Petasis, Nicolas G. BazanAbstract:Docosahexaenoic acid (DHA, 22:6 n-3) is abundant in the retina and is enzymatically converted into pro-homeostatic Docosanoids. The DHA- or eicosapentaenoic acid (EPA)-derived 26 carbon fatty acid is a substrate of elongase ELOVL4, which is expressed in photoreceptor cells and generates very long chain (≥C28) polyunsaturated fatty acids including n-3 (VLC-PUFAs,n-3). While ELOVL4 mutations are linked to vision loss and neuronal dysfunctions, the roles of VLC-PUFAs remain unknown. Here we report a novel class of lipid mediators biosynthesized in human retinal pigment epithelial (RPE) cells that are oxygenated derivatives of VLC-PUFAs,n-3; we termed these mediators elovanoids (ELV). ELVs have structures reminiscent of Docosanoids but with different physicochemical properties and alternatively-regulated biosynthetic pathways. The structures, stereochemistry, and bioactivity of ELVs were determined using synthetic materials produced by stereo-controlled chemical synthesis. ELVs enhance expression of pro-survival proteins in cells undergoing uncompensated oxidative stress. Our findings unveil a novel autocrine/paracrine pro-homeostatic RPE cell signaling that aims to sustain photoreceptor cell integrity and reveal potential therapeutic targets for retinal degenerations.
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Thematic Minireview Series: Inflammatory transcription confronts homeostatic disruptions
The Journal of biological chemistry, 2017Co-Authors: Nicolas G. Bazan, George M. CarmanAbstract:In this Thematic Minireview Series, three stimulating articles are presented: one on long non-coding RNAs, another on the ligand-activated transcription factor aryl hydrocarbon receptor, and the third on how Docosanoids modulate transcriptionally modulated homeostasis and ultimately cell survival in the retina and brain.
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Molecular mechanisms of signaling via the Docosanoid neuroprotectin D1 for cellular homeostasis and neuroprotection.
The Journal of biological chemistry, 2017Co-Authors: Aram Asatryan, Nicolas G. BazanAbstract:Docosahexaenoic acid, enriched in the brain and retina, generates Docosanoids in response to disruptions of cellular homeostasis. Docosanoids include neuroprotectin D1 (NPD1), which is decreased in the CA1 hippocampal area of patients with early-stage Alzheimer's disease (AD). We summarize here how NPD1 elicits neuroprotection by up-regulating c-REL, a nuclear factor (NF)-κB subtype that, in turn, enhances expression of BIRC3 (baculoviral inhibitor of apoptosis repeat-containing protein 3) in the retina and in experimental stroke, leading to neuroprotection. Elucidating the mechanisms of action of Docosanoids will contribute to managing diseases, including stroke, AD, age-related macular degeneration, traumatic brain injury, Parkinson's disease, and other neurodegenerations.
Robert C Murphy - One of the best experts on this subject based on the ideXlab platform.
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formation of eicosanoids e2 d2 isoprostanes and Docosanoids following decapitation induced ischemia measured in high energy microwaved rat brain
Journal of Lipid Research, 2008Co-Authors: Santiago E Farias, Mireille Basselin, Lisa Chang, Kim A Heidenreich, Stanley I Rapoport, Robert C MurphyAbstract:Inflammatory lipid mediators derived from arachidonic acid (AA) and docosahexaenoic acid (DHA) modify the pathophysiology of brain ischemia. The goal of this work was to investigate the formation of eicosanoids and Docosanoids generated from AA and DHA, respectively, during no-flow cerebral ischemia. Rats were subjected to head-focused microwave irradiation 5 min following decapitation (complete ischemia) or prior to decapitation (controls). Brain lipids were extracted and analyzed by reverse-phase liquid chromatography-tandem mass spectrometry. After complete ischemia, brain AA, DHA, and docosapentaenoic acid concentrations increased 18-, 5- and 4-fold compared with controls, respectively. Prostaglandin E2 (PGE2) and PGD2 could not be detected in control microwaved rat brain, suggesting little endogenous PGE2/D2 production in the brain in the absence of experimental manipulation. Concentrations of thromboxane B2, E2/D2-isoprostanes, 5-hydroxyeicosatetraenoic acid (5-HETE), 5-oxo-eicosatetraenoic acid, and 12-HETE were significantly elevated in ischemic brains. In addition, DHA products such as mono-, di- and trihydroxy-DHA were detected in control and ischemic brains. Monohydroxy-DHA, identified as 17-hydroxy-DHA and thought to be the immediate precursor of neuroprotectin D1, was 6.5-fold higher in ischemic than in control brain. The present study demonstrated increased formation of eicosanoids, E2/D2-IsoPs, and Docosanoids following cerebral ischemia. A balance of these lipid mediators may mediate immediate events of ischemic injury and recovery.
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Formation of eicosanoids, E2/D2 isoprostanes, and Docosanoids following decapitation-induced ischemia, measured in high-energy-microwaved rat brain.
Journal of lipid research, 2008Co-Authors: Santiago E Farias, Mireille Basselin, Lisa Chang, Kim A Heidenreich, Stanley I Rapoport, Robert C MurphyAbstract:Inflammatory lipid mediators derived from arachidonic acid (AA) and docosahexaenoic acid (DHA) modify the pathophysiology of brain ischemia. The goal of this work was to investigate the formation of eicosanoids and Docosanoids generated from AA and DHA, respectively, during no-flow cerebral ischemia. Rats were subjected to head-focused microwave irradiation 5 min following decapitation (complete ischemia) or prior to decapitation (controls). Brain lipids were extracted and analyzed by reverse-phase liquid chromatography-tandem mass spectrometry. After complete ischemia, brain AA, DHA, and docosapentaenoic acid concentrations increased 18-, 5- and 4-fold compared with controls, respectively. Prostaglandin E2 (PGE2) and PGD2 could not be detected in control microwaved rat brain, suggesting little endogenous PGE2/D2 production in the brain in the absence of experimental manipulation. Concentrations of thromboxane B2, E2/D2-isoprostanes, 5-hydroxyeicosatetraenoic acid (5-HETE), 5-oxo-eicosatetraenoic acid, and 12-HETE were significantly elevated in ischemic brains. In addition, DHA products such as mono-, di- and trihydroxy-DHA were detected in control and ischemic brains. Monohydroxy-DHA, identified as 17-hydroxy-DHA and thought to be the immediate precursor of neuroprotectin D1, was 6.5-fold higher in ischemic than in control brain. The present study demonstrated increased formation of eicosanoids, E2/D2-IsoPs, and Docosanoids following cerebral ischemia. A balance of these lipid mediators may mediate immediate events of ischemic injury and recovery.
Haydee E. P. Bazan - One of the best experts on this subject based on the ideXlab platform.
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Docosanoid signaling modulates corneal nerve regeneration: effect on tear secretion, wound healing, and neuropathic pain.
Journal of lipid research, 2021Co-Authors: Thang Luong Pham, Haydee E. P. BazanAbstract:The cornea is densely innervated, mainly by sensory nerves of the ophthalmic branch of the trigeminal ganglia (TG). These nerves are important to maintain corneal homeostasis, and nerve damage can lead to a decrease in wound healing, an increase in corneal ulceration and dry eye disease (DED), and neuropathic pain. Pathologies, such as diabetes, aging, viral and bacterial infection, as well as prolonged use of contact lenses and surgeries to correct vision can produce nerve damage. There are no effective therapies to alleviate DED (a multifunctional disease) and several clinical trials using ω-3 supplementation show unclear and sometimes negative results. Using animal models of corneal nerve damage, we show that treating corneas with pigment epithelium-derived factor (PEDF) plus docosahexaenoic acid (DHA) increases nerve regeneration, wound healing, and tear secretion. The mechanism involves the activation of a calcium-independent phospholipase A2 (iPLA2ζ) that releases the incorporated DHA from phospholipids and enhances the synthesis of Docosanoids neuroprotectin D1 (NPD1) and a new resolvin stereoisomer RvD6i. NPD1 stimulates the synthesis of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and of semaphorin 7A (Sema7A). RvD6i treatment of injured corneas modulates gene expression in the TG resulting in enhanced neurogenesis; decreased neuropathic pain and increased sensitivity. Taken together, these results represent a promising therapeutic option to re-establish the homeostasis of the cornea.
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Involvement of pigment epithelium-derived factor, docosahexaenoic acid and neuroprotectin D1 in corneal inflammation and nerve integrity after refractive surgery.
Prostaglandins leukotrienes and essential fatty acids, 2012Co-Authors: Sachidananda Kenchegowda, Haydee E. P. BazanAbstract:Alterations in corneal innervations result in impaired corneal sensation, severe dry eye and damage to the epithelium that may in turn lead to corneal ulcers, melting and perforation. These alterations can occur after refractive surgery. We have discovered that pigment epithelium-derived factor (PEDF) plus docosahexaenoic acid (DHA or the Docosanoid bioactive neuroprotectin D1 (NPD1)) induces nerve regeneration after corneal surgery that damages the stromal nerves. We found that PEDF is released from corneal epithelial cells after injury, and when DHA is provided to the cells it stimulates the biosynthesis of NPD1 by an autocrine mechanism. The combination of PEDF plus DHA also decreased the production of leukotriene B4 (LTB4), a neutrophil chemotactic factor, thereby decreasing the inflammation induced after corneal damage. These studies suggest that PEDF plus DHA and its derivative NPD1 hold promise as a future treatment to restore a healthy cornea after nerve damage.
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Omega-3 fatty acids in dry eye and corneal nerve regeneration after refractive surgery.
Prostaglandins Leukotrienes and Essential Fatty Acids, 2010Co-Authors: Haydee E. P. BazanAbstract:Dry eye (DE) is a multifactorial condition that affects the surface of the eye and induces an inflammatory response. Corneal nerves play an important role in the maintenance of a healthy ocular surface. Here we review corneal structure, nerve architecture, DE conditions, and nerve regeneration following corneal surgery and discuss how n-3 fatty acids affect the health of the cornea. Animal studies show that resolvins, compounds derived from eicosapentaenoic acid (EPA), increase tear volume and decrease inflammation induced by DE. After corneal surgery in rabbits, treatment with nerve growth factor (NGF) or pigment epithelial derived factor (PEDF) in conjunction with docosahexaenoic acid (DHA) increase nerve density and corneal epithelial cell proliferation. Increased synthesis of the novel Docosanoid, neuroprotectin D1 (NPD1), was found in corneas after the animals were treated with PEDF and DHA. Topical application of these lipids derived from n-3 fatty acids could be useful in treating DE and prevent clinical complications such as cornea erosion and ulcerations.
Santiago E Farias - One of the best experts on this subject based on the ideXlab platform.
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formation of eicosanoids e2 d2 isoprostanes and Docosanoids following decapitation induced ischemia measured in high energy microwaved rat brain
Journal of Lipid Research, 2008Co-Authors: Santiago E Farias, Mireille Basselin, Lisa Chang, Kim A Heidenreich, Stanley I Rapoport, Robert C MurphyAbstract:Inflammatory lipid mediators derived from arachidonic acid (AA) and docosahexaenoic acid (DHA) modify the pathophysiology of brain ischemia. The goal of this work was to investigate the formation of eicosanoids and Docosanoids generated from AA and DHA, respectively, during no-flow cerebral ischemia. Rats were subjected to head-focused microwave irradiation 5 min following decapitation (complete ischemia) or prior to decapitation (controls). Brain lipids were extracted and analyzed by reverse-phase liquid chromatography-tandem mass spectrometry. After complete ischemia, brain AA, DHA, and docosapentaenoic acid concentrations increased 18-, 5- and 4-fold compared with controls, respectively. Prostaglandin E2 (PGE2) and PGD2 could not be detected in control microwaved rat brain, suggesting little endogenous PGE2/D2 production in the brain in the absence of experimental manipulation. Concentrations of thromboxane B2, E2/D2-isoprostanes, 5-hydroxyeicosatetraenoic acid (5-HETE), 5-oxo-eicosatetraenoic acid, and 12-HETE were significantly elevated in ischemic brains. In addition, DHA products such as mono-, di- and trihydroxy-DHA were detected in control and ischemic brains. Monohydroxy-DHA, identified as 17-hydroxy-DHA and thought to be the immediate precursor of neuroprotectin D1, was 6.5-fold higher in ischemic than in control brain. The present study demonstrated increased formation of eicosanoids, E2/D2-IsoPs, and Docosanoids following cerebral ischemia. A balance of these lipid mediators may mediate immediate events of ischemic injury and recovery.
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Formation of eicosanoids, E2/D2 isoprostanes, and Docosanoids following decapitation-induced ischemia, measured in high-energy-microwaved rat brain.
Journal of lipid research, 2008Co-Authors: Santiago E Farias, Mireille Basselin, Lisa Chang, Kim A Heidenreich, Stanley I Rapoport, Robert C MurphyAbstract:Inflammatory lipid mediators derived from arachidonic acid (AA) and docosahexaenoic acid (DHA) modify the pathophysiology of brain ischemia. The goal of this work was to investigate the formation of eicosanoids and Docosanoids generated from AA and DHA, respectively, during no-flow cerebral ischemia. Rats were subjected to head-focused microwave irradiation 5 min following decapitation (complete ischemia) or prior to decapitation (controls). Brain lipids were extracted and analyzed by reverse-phase liquid chromatography-tandem mass spectrometry. After complete ischemia, brain AA, DHA, and docosapentaenoic acid concentrations increased 18-, 5- and 4-fold compared with controls, respectively. Prostaglandin E2 (PGE2) and PGD2 could not be detected in control microwaved rat brain, suggesting little endogenous PGE2/D2 production in the brain in the absence of experimental manipulation. Concentrations of thromboxane B2, E2/D2-isoprostanes, 5-hydroxyeicosatetraenoic acid (5-HETE), 5-oxo-eicosatetraenoic acid, and 12-HETE were significantly elevated in ischemic brains. In addition, DHA products such as mono-, di- and trihydroxy-DHA were detected in control and ischemic brains. Monohydroxy-DHA, identified as 17-hydroxy-DHA and thought to be the immediate precursor of neuroprotectin D1, was 6.5-fold higher in ischemic than in control brain. The present study demonstrated increased formation of eicosanoids, E2/D2-IsoPs, and Docosanoids following cerebral ischemia. A balance of these lipid mediators may mediate immediate events of ischemic injury and recovery.
Gert Heinrich - One of the best experts on this subject based on the ideXlab platform.
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pre intercalation of long chain fatty acid in the interlayer space of layered silicates and preparation of montmorillonite natural rubber nanocomposites
Applied Clay Science, 2012Co-Authors: Sandip Rooj, Amit Das, Klaus Werner Stöckelhuber, Nabaneeta Mukhopadhyay, Arup R. Bhattacharyya, Dieter Jehnichen, Gert HeinrichAbstract:Abstract A series of long chain fatty acids was intercalated into the interlayer space of organo montmorillonite (OMt) and a gradual expansion of the interlayer space was observed as the chain length of the fatty acid increased. The fatty acid with 22 carbon atoms (docosanoic acid) was found to offer a highest interlayer space among the fatty acids under consideration. This fatty acid was selected further to modify OMt and subsequently utilized as reinforcing fillers in natural rubber (NR) matrix. Wide angle X-ray diffraction (WAXD), Fourier transform infrared (FTIR) spectroscopy and contact angle measurement indicated successful intercalation of the fatty acid into the interlayer space of the clay minerals. The main objective of such intercalation is to make clay minerals suitable for the preparation of rubber nanocomposites, especially when using non-polar rubbers. Docosanoic acid intercalated Mt was successfully dispersed in NR matrix as confirmed by WAXD and transmission electron microscopy (TEM). As a result, the mechanical properties were found to be improved in a remarkable way. Improvement of ~ 114% in tensile strength and ~ 203% in modulus at 300% elongation was observed. These results were correlated with the morphological data obtained from WAXD and TEM.
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Pre-intercalation of long chain fatty acid in the interlayer space of layered silicates and preparation of montmorillonite/natural rubber nanocomposites
Applied Clay Science, 2012Co-Authors: Sandip Rooj, Amit Das, Klaus Werner Stöckelhuber, Nabaneeta Mukhopadhyay, Arup R. Bhattacharyya, Dieter Jehnichen, Gert HeinrichAbstract:Abstract A series of long chain fatty acids was intercalated into the interlayer space of organo montmorillonite (OMt) and a gradual expansion of the interlayer space was observed as the chain length of the fatty acid increased. The fatty acid with 22 carbon atoms (docosanoic acid) was found to offer a highest interlayer space among the fatty acids under consideration. This fatty acid was selected further to modify OMt and subsequently utilized as reinforcing fillers in natural rubber (NR) matrix. Wide angle X-ray diffraction (WAXD), Fourier transform infrared (FTIR) spectroscopy and contact angle measurement indicated successful intercalation of the fatty acid into the interlayer space of the clay minerals. The main objective of such intercalation is to make clay minerals suitable for the preparation of rubber nanocomposites, especially when using non-polar rubbers. Docosanoic acid intercalated Mt was successfully dispersed in NR matrix as confirmed by WAXD and transmission electron microscopy (TEM). As a result, the mechanical properties were found to be improved in a remarkable way. Improvement of ~ 114% in tensile strength and ~ 203% in modulus at 300% elongation was observed. These results were correlated with the morphological data obtained from WAXD and TEM.