ALOX15 (Arachidonate 15-Lipoxygenase)

Pharmacological analyses demonstrated that these anti-inflammatory effects were mediated via Gαq-dependent G protein-coupled receptor signaling and downstream activation of phospholipase C and protein kinase C. Notably, 12-HETE required Ca2+-dependent conventional PKCs, whereas 13-HODE selectively involved PKCε. Together, our findings identify ALOX15-derived oxylipins as endogenous regulators that attenuate macrophage inflammatory signaling via a Gαq-PLC-PKC pathway, providing mechanistic insight into lipid-mediated control of intestinal inflammation.

Western blot analysis further confirmed that ALOX15 inhibits HNSC progression via the ERK pathway. In summary, ALOX15 may serve as a potential biomarker across multiple cancer types.

SEO exerts antidepressant-like effects in BCRD by modulating hippocampus-centered metabolic and functional networks. Eugenol and 2-phenylethanol were identified as key brain-entry components to function through metabolic pathways. ALOX15 inhibition and CAII improvement were proven to be the main molecular mechanisms. These findings provide mechanistic insights and identify SEO as a promising plant-derived therapeutic candidate for managing cancer-related depression.

Mammalian ALOX15 orthologs are allosteric enzymes but the molecular basis for their allosteric properties remains controversial. In fact, two alternative hypotheses (presence of allosteric binding sites at enzyme monomers vs. ALOX15 dimers consist of an allosteric and a catalytic monomer) have been introduced and this review is aimed at critically evaluating the pros and conts of these two mechanistic scenarios.

Notably, elevated PKCβ levels enhance the efficacy of ferroptosis-inducing cancer therapies, while inhibition of the Ca2 +-PKCβ signaling pathway protects against acute pancreatitis by suppressing ferroptosis. These findings underscore the therapeutic potential of targeting Ca2 +-PKCβ-mediated ferroptosis, offering new avenues for the treatment of cancer and acute pancreatitis.

Key prognostic genes, including SLC2A1, SLC16A1, IL1A, AHSG, and ALOX15, were validated through RT-qPCR. This study highlights the molecular heterogeneity of propionate metabolism in LUAD and proposes a prognostic signature that could inform immunotherapeutic stratification.

Multivariate COX regression analysis demonstrated that DLGAP1 was an independent prognostic factor for PAAD. Six hub genes might exert an influence on the initial lymphatic metastasis of PAAD through immune cell infiltration and ferroptosis.

ZLN suppresses CEC ferroptosis by inhibiting ALOX15/15(S)-HPETE to repress colorectal tumorigenesis and progression, providing a rationale for employing ZLN as a potential therapeutic approach.

Concurrently, VEGF downregulation and p53 upregulation reflected additional anti-angiogenic and pro-apoptotic effects. Collectively, the lactoferrin-functionalized Nic-NLC produced the most robust antitumor response, with superior ferroptosis induction, redox modulation, and anti-angiogenic activity.

AS601245, AP.24534 and roscovitine were the top three chemotherapeutic agents showing the highest sensitivity differences between the risk groups. The RT-qPCR results indicated that the expression of electron transfer flavoprotein subunit α, rap guanine nucleotide exchange factor-like 1, keratin 7, cluster of differentiation 24, proline rich 15-like, arachidonate 15-lipoxygenase type B, ELOVL fatty acid elongase 2 and C-X-C motif chemokine ligand 9 was consistent with the results of bioinformatic analysis. In conclusion, the HER2-related risk model and nomogram developed in the present study demonstrated high accuracy in predicting patient survival.

Similarly, SCDA also increased levels of the antioxidant glutathione (GSH), which is associated with inhibition of P53 and promotion of the expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), resulting in an improved balance between antioxidant and oxidant systems. This provides new drugs and targets for the treatment of right ventricular hypertrophy.

ALOX15 could exacerbates high-altitude hypoxic ALI inflammatory responses by promoting both macrophage ferroptosis and M1 polarization. Identification of baicalein as an ALOX15 inhibitor mitigates ferroptosis, shifts macrophages to the M2 phenotype, and reduces inflammation, offering a promising preventative strategy for high-altitude hypoxic lung injury.