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Sphingolipids in COPD

Raja Chandra Chakinala, Akshay Khatri, Kriti Gupta, Kengo Koike, Oleg Epelbaum
European Respiratory Review 2019 28: 190047; DOI: 10.1183/16000617.0047-2019
Raja Chandra Chakinala
1Dept of Medicine, Westchester Medical Center, Valhalla, NY, USA
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Akshay Khatri
1Dept of Medicine, Westchester Medical Center, Valhalla, NY, USA
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Kriti Gupta
2Dept of Medicine, Maimonides Medical Center, New York, NY, USA
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Kengo Koike
3Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, CO, USA
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Oleg Epelbaum
4Division of Pulmonary, Critical Care and Sleep Medicine, Westchester Medical Center, Valhalla, NY, USA
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  • FIGURE 1
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    FIGURE 1

    a) Schematic depiction of the three major pathways capable of producing ceramide with relevant enzymes (italics) and therapeutic inhibition points (arrows) indicated. b) Schematic representation of the three major reactions involving ceramide as substrate. Relevant enzymes are listed in italics, and options for so-called “sphingosine 1-phosphate rescue” are indicated by arrows. −: inhibitory actions; +: promoter actions.

  • FIGURE 2
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    FIGURE 2

    Competing sphingolipids with predominantly pro-inflammatory and anti-inflammatory properties, the net balance of which constitutes the “sphingolipid rheostat”.

  • FIGURE 3
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    FIGURE 3

    Schematic summary of sphingolipid actions implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD) with ceramide as the central mediator. C1P: ceramide 1-phosphate; S1P: sphingosine 1-phosphate; nSMase: neutral sphingomyelinase; ROS: reactive oxygen species; SOD: superoxide dismutase; TNF-α: tumour necrosis factor-α. +: pro-inflammatory effects of ceramide derivatives; −: anti-inflammatory.

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European Respiratory Review: 28 (154)
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Sphingolipids in COPD
Raja Chandra Chakinala, Akshay Khatri, Kriti Gupta, Kengo Koike, Oleg Epelbaum
European Respiratory Review Dec 2019, 28 (154) 190047; DOI: 10.1183/16000617.0047-2019

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Sphingolipids in COPD
Raja Chandra Chakinala, Akshay Khatri, Kriti Gupta, Kengo Koike, Oleg Epelbaum
European Respiratory Review Dec 2019, 28 (154) 190047; DOI: 10.1183/16000617.0047-2019
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  • Article
    • Abstract
    • Abstract
    • Introduction
    • Sphingolipid biochemistry
    • Sphingolipids and COPD pathogenesis
    • Therapeutic implications
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