OL targets ACOT1 and promotes its Ub‒proteasome degradation to exert therapeutic effects (all groups, n = 3; *p < 0.05, **p < 0.01; data are presented as the mean ± SD). (IMAGE)
Caption
(a) The CHX chase assay demonstrated that OL significantly decreased the protein stability of ACOT1 (p < 0.05), suggesting that OL regulated ACOT1 expression via a posttranslational mechanism. (b) This hypothesis was supported by the observation that the proteasome inhibitor MG132 effectively blocked OL-induced ACOT1 degradation. (c) OL reduces ACOT1 expression through the ubiquitinated protease degradation pathway. (d) The therapeutic mechanism of OL in RA: OL binds to ACOT1 and promotes its degradation via the Ub‒proteasome pathway. The subsequent reduction in ACOT1 expression and activity diminishes the production of free fatty acids, including proinflammatory unsaturated fatty acids and their metabolites (e.g., AA, LTB4, PGE2, and 5-HETE). This correction of unsaturated fatty acid biosynthesis and metabolism inhibits the activation of the PI3K–AKT/JAK–STAT signaling pathway, thereby suppressing aberrant SF proliferation and joint deformity. Concurrently, it reduces the release of proinflammatory and tissue-damaging factors, ultimately alleviating joint inflammation and damage.
Credit
Hongda Liu, Le Yang et al.
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