Formation and electrophysiological actions of the arachidonic acid metabolites, hepoxilins, at nanomolar concentrations in rat hippocampal slices
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The ALOXE3 gene variants from patients with Dravet syndrome decrease gene expression and enzyme activity
2021, Brain Research BulletinCitation Excerpt :For example, free AA was accumulated in the brain under seizure condition (Bazan et al., 1986; Lerner et al., 2017), which was identified to enhance the neuronal excitability by promoting the release of glutamate from glial cells (Zeldin, 2001), or by inhibiting potassium ion channels (Bringmann et al., 1998; Villarroel and Schwarz, 1996) and GABA-gated chloride channels (Schwartz RD, 1992). In addition, the AA metabolites such as hepoxilins could increase intracellular calcium in neurons (Amer et al., 2003) and were involved in the regulation of inhibitory postsynaptic potential (Carlen et al., 1994), implicating important roles of the AA metabolites in the epileptogenesis. Furthermore, a critical enzyme cyclooxygenase-2 (COX-2) in the AA cascade potentially contributes to epileptic seizures.
Pathophysiology of the hepoxilins
2015, Biochimica et Biophysica Acta - Molecular and Cell Biology of LipidsCitation Excerpt :Although it would be expected that hepoxilins would not be formed in 12-LOX knockout mice, it is possible that these compounds may be formed through pathways other than the classical AA cascade (see section on Skin). There is limited information regarding the potential role of hepoxilins in the brain except that the hepoxilins are formed in the brain and that they modulate electrical and neurotransmitter effects [108]. Hepoxilin A3 was shown to potentiate neurite regeneration [109].
Mammalian soluble epoxide hydrolase is identical to liver hepoxilin hydrolase
2011, Journal of Lipid ResearchAn integrated omics analysis of eicosanoid biology
2009, Journal of Lipid ResearchCitation Excerpt :The epoxy moiety is labile and can be hydrolyzed either by a hepoxilin specific epoxide hydrolase (HXEH) (118) or in acidic aqueous solution to form the corresponding diol metabolites trioxilin A3 and B3 (117). Most of the known bioactive effects can be attributed to HXA3, which include intracellular calcium release (119), neutrophil migration (120), insulin secretion (121), ichthyosis (122), and modulation of neuronal signaling (123). Current evidence suggests the existence of a HXA3 receptor (124), but to date one has not been identified.
Tocotrienols in health and disease: The other half of the natural vitamin E family
2007, Molecular Aspects of Medicine