induction of pro-carcinogenic 12-LOX pathway by an anticancer ceramide, which may be relevant to cancer biologists studying drug resistant tumors and devising potent anticancer therapeutic strategies to treat drug resistant tumors. Induction of 12-LOX pathway by ceramide may have implications in understanding pathophysiology of neurodegenerative diseases involving reactive oxygen species generation and inflammation
the 12/15-LOX metabolic pathway is increased and correlates with an oxidative imbalance in the Alzheimers disease brain, implying that this enzyme might contribute to the pathogenesis of this neurodegenerative disorder. Thus, drugs that specifically reduce or block the 12/15-LOX metabolic pathway activation may warrant consideration as potential therapeutic interventions for Alzheimers disease
psoralen plus ultraviolet A decreases 12-LOX expression, thus this UVA photochemotherapy is considered to be first-line treatment for patients with moderate to severe psoriasis. Interruption of 12-LOX catalytic activity and the 12-hydroxyeicosatetraenoic acid signaling pathway by increasing 15-LOX metabolites may be a promising target for psoriasis therapies
15 lipoxygenase 1 is abundant in asthmatic human airway epithelial cells and binds phosphatidylethanolamine-binding protein 1 (PEBP1), leading to generation of hydroperoxy-phospholipids, which drive ferroptotic cell death. 15LO1, PEBP1, and glutathione peroxidase 4 GPX4 activity drives abnormal asthmatic redox biology, to enhance type 2 inflammatory responses. In vitro, type 2 inflammatory cytokine IL-13 induces 15LO1 generation of hydroperoxy-phospholipids, which lowers intracellular GSH and increased extracellular GSSG levels. Lowering GSH further by inhibiting cystine transporter SLC7A11 enhances type 2 inflammatory protein expression and ferroptosis. Ex vivo, redox imbalances correspond to 15LO1 and SLC7A11 expression, type 2 inflammatory biomarkers, and worsen clinical outcomes
activity of 12S-lipoxygenase is hardly observed in liver cytosol of normal chow-fed mice but is clearly detectable in that of nonalcoholic steatohepatitis model mice prepared by feeding a methionine and choline-deficient diet
application of 14(S)-hydroxy docosahexaenoic acid suppresses IL-33-mediated eosinophilic inflammation in 12/15-LOX-deficient mice. 14(S)-hydroxy docosahexaenoic acid and 10(S),17(S)-dihydroxy docosahexaenoic acid markedly attenuate ILC2 proliferation and cytokine production at micromolar concentration in vitro. Maresin 1 (MaR1) and resolvin D1 (RvD1), 12/15-LOX-derived specialized proresolving mediators (SPMs), inhibited cytokine production of ILC2s at nanomolar concentration
humans acutely treated with specific beta3-adrenergic agonist mirabegron display elevated levels of 12-LOX metabolites in the circulation, and significantly higher levels of 12-hydroxyeicosapentaenoic acid and 14-hydroxydocosahexaenoic acid are found in the media of brown adipocytes treated with the beta3-adrenergic agonist CL316,243 for 4 hours
hypoxia increases the formation of endogenous 12-hydroxyeicosatetraenoic acid through stimulation of 12-lipoxygenase. 12-hydroxyeicosatetraenoic acid promotes endothelial cell migration and tube formation, whereas it inhibits the serum deprivation-induced apoptotic responses under hypoxia. The regulatory effects of 12-lipoxygenase/12-hydroxyeicosatetraenoic acid on pulmonary artery endothelial cells, at least in part, depend on phosphatidylinositol 3-kinase (PI3K)/Akt signaling activatio
older normal human fibroblasts (NHFs) have significantly increased arachidonic acid 12-lipoxygenase (ALOX12) expression and elevated levels of its mitogenic metabolite, 12-(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12-(S)-HETE) compared with their younger counterparts. In cocultures with older rather than with younger NHFs, pancreatic ductal adenocarcinoma cells exhibit increases in mitogen-activated protein kinase signaling and cellular metabolism, as well as a lower oxidation state that correlates with their enhanced proliferation and resistance to radiation therapy. Expression of ALOX12 is significantly lower in pancreatic ductal adenocarcinoma cell lines and tumor biopsies
Streptococcus pneumoniae infection of the respiratory epithelium induces the production of the 12-lipoxygenase-dependent lipid inflammatory mediator hepoxilin A3, which promotes recruitment of neutrophils into the airways, tissue damage, and lethal septicemia. A pneumolysin-deficient S. pneumoniae mutant is impaired in triggering human neutrophil transepithelial migration in vitro
Streptococcus pneumoniae infection of the respiratory epithelium induces the production of the 12-lipoxygenase-dependent lipid inflammatory mediator hepoxilin A3, which promotes recruitment of neutrophils into the airways, tissue damage, and lethal septicemia. A pneumolysin-deficient S. pneumoniae mutant is impaired in triggering human neutrophil transepithelial migration in vitro
when treating type 2 diabetic wild-type mice and transgenic mice ubiquitously overexpressing 15-LOX-1 with menhaden (fish) oil, there is a trend for the severity of diabetic peripheral neuropathy-related deficits to be less in the diabetic transgenic mice compared to the diabetic wild-type mice. Treating diabetic wild-type and transgenic mice with menhaden oil improves the diabetic peripheral neuropathy-related endpoints with a trend for greater improvement or protection by menhaden oil observed in the diabetic transgenic mice