Achieving Life through Death: Redox Biology of Lipid Peroxidation in Ferroptosis
CELL CHEMICAL BIOLOGY
Authors: Bayir, Hulya; Anthonymuthu, Tamil S.; Tyurina, Yulia Y.; Patel, Sarju J.; Amoscato, Andrew A.; Lamade, Andrew M.; Yang, Qin; Vladimirov, Georgy K.; Philpott, Caroline C.; Kagan, Valerian E.
Abstract
Redox balance is essential for normal brain, hence dis-coordinated oxidative reactions leading to neuronal death, including programs of regulated death, are commonly viewed as an inevitable pathogenic penalty for acute neuro-injury and neurodegenerative diseases. Ferroptosis is one of these programs triggered by dyshomeostasis of three metabolic pillars: iron, thiols, and polyunsaturated phospholipids. This review focuses on: (1) lipid peroxidation (LPO) as the maim instrument of cell demise, (2) iron as its catalytic mechanism, and (3) thiols as regulators of pro-ferroptotic signals, hydroperoxy lipids. Given the central role of LPO, we discuss the engagement of selective and specific enzymatic pathways versus random free radical chemical reactions in the context of the phospholipid substrates, their biosynthesis, intracellular location, and related oxygenating machinery as participants in ferroptotic cascades. These concepts are discussed in the light of emerging neuro-therapeutic approaches controlling intracellular production of pro-ferroptotic phospholipid signals and their non-cell-autonomous spreading, leading to ferroptosis-associated necroin-flammation.
Sub-pathway analysis for severe burns injury patients: Identification of potential key lncRNAs by analyzing lncRNA-mRNA
EXPERIMENTAL AND THERAPEUTIC MEDICINE
Authors: Tang, Gongjie; Zhang, Tao; Wang, Xinbo; Song, Zengmei; Liu, Fucun; Zhang, Qian; Huo, Ran
Abstract
The aim of the study was to identify key long non-coding RNAs (lncRNA) and related subpathways following severe burn injuries and research their functions. The miRNA-mRNA and lncRNA-miRNA interactions were downloaded from starBase v2.0 database. In addition, mRNA-miRNA interactions were obtained from TarBase, mirTarBase, mir2Disease, miRecords (V4.0) databases. The relationships of lncRNA-miRNA-mRNA were constructed. Genes of expression profiling were intersected with mRNA and lncRNA in lncRNA-mRNA interaction. Screened mRNAs were enriched into various pathways and screened lncRNAs were embedded into candidate pathways. Wallenius approximation methods were used to calculate the false discovery rate value of each sub-pathway. Based on the results of significant sub-pathways, the related lncRNA-mRNA network was constructed. A total of 18,081 genes were obtained. The lncRNA-mRNA intersections including 835 lncRNAs, 1,749 mRNAs and 7,693 interacting pairs were constructed. The enriched mRNAs were further enriched into various candidate pathways such as ribosome biogenesis in eukaryotes. Several sub-pathways were screened, including ribosome biogenesis in eukaryotes and MAPK signaling pathway. The network of pathway-lncRNA-mRNA was constructed. Hub-genes were identified, including C14orf169 and YLPM1. Several hub-lncRNAs were obtained, including PRKAG2 antisense RNA 1 and LEF1 antisense RNA 1. Several hub-lncRNAs including C14orf169, YLPM1, TTTY15, and PCBP1-AS1 were screened. The sub-pathways regulated by these lncRNAs were identified, and functions were predicted.