Hypoxic-Ischemic Encephalopathy

Fink, Ericka L.; Clark, Robert S. B.; Kochanek, Patrick M.

doi:10.1016/b978-0-323-07307-3.10062-x

Cited by 1 publication

(1 citation statement)

References 339 publications

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“…Moreover, lipids are also known to modulate the activity of voltage-gated ion channels including calcium channel and G protein–signaling mechanisms [ 83 , 84 ]. As previously mentioned, phospholipases such as cPLA2 hydrolyze glycerophospholipids by binding to membrane G-protein-coupled receptors and releasing free fatty acids, such as AA and LA, from the membrane [ 85 , 86 ]. Our pathway analysis of differentially expressed genes confirmed the involvement of ion channels and bioactive lipids signaling pathways during HDM sensitization.…”

Section: Discussionmentioning

confidence: 99%

Multi-Omics Analysis of Lung Tissue Demonstrates Changes to Lipid Metabolism during Allergic Sensitization in Mice

et al. 2023

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Allergy and asthma pathogenesis are associated with the dysregulation of metabolic pathways. To understand the effects of allergen sensitization on metabolic pathways, we conducted a multi-omics study using BALB/cJ mice sensitized to house dust mite (HDM) extract or saline. Lung tissue was used to perform untargeted metabolomics and transcriptomics while both lung tissue and plasma were used for targeted lipidomics. Following statistical comparisons, an integrated pathway analysis was conducted. Histopathological changes demonstrated an allergic response in HDM-sensitized mice. Untargeted metabolomics showed 391 lung tissue compounds were significantly different between HDM and control mice (adjusted p < 0.05); with most compounds mapping to glycerophospholipid and sphingolipid pathways. Several lung oxylipins, including 14-HDHA, 8-HETE, 15-HETE, 6-keto-PGF1α, and PGE2 were significantly elevated in HDM-sensitized mice (p < 0.05). Global gene expression analysis showed upregulated calcium channel, G protein–signaling, and mTORC1 signaling pathways. Genes related to oxylipin metabolism such as Cox, Cyp450s, and cPla2 trended upwards. Joint analysis of metabolomics and transcriptomics supported a role for glycerophospholipid and sphingolipid metabolism following HDM sensitization. Collectively, our multi-omics results linked decreased glycerophospholipid and sphingolipid compounds and increased oxylipins with allergic sensitization; concurrent upregulation of associated gene pathways supports a role for bioactive lipids in the pathogenesis of allergy and asthma.

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