MG-149

Acute lung injury (ALI) remains a life-threatening condition characterized by excessive inflammation and oxidative stress. This study aimed to investigate the role of Lysine acetyltransferase 8 (KAT8) in lipopolysaccharide (LPS)-induced ALI and explore its underlying molecular mechanisms.

Gene and protein expression were analyzed via RT-qPCR and Western blot. Molecular interactions were validated using Co-immunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP), and luciferase reporter assays. Lung histopathology was evaluated by H&E staining. Oxidative stress markers (SOD, MPO, MDA, ROS) were quantified.

KAT8 expression was elevated in LPS-treated cells and lung tissues. Genetic silencing of KAT8 attenuated LPS-induced inflammatory cytokine secretion, oxidative stress, and NLRP3 inflammasome activation. Mechanistically, KAT8 promoted p53 acetylation, enhancing its binding to the NLRP3 promoter and upregulating its transcription. Conversely, p53 knockdown abolished KAT8-mediated inflammatory cytokine secretion, oxidative stress, and NLRP3 inflammasome activation in LPS-induced ALI. In vivo, pharmacological inhibition of KAT8 with MG149 alleviated LPS-induced ALI as evidenced by reduced neutrophil infiltration, pulmonary edema, and oxidative damage. Concurrently, MG149 suppressed p53 acetylation and NLRP3 activation in murine lungs.

This study identifies KAT8 as a key epigenetic regulator driving LPS-induced ALI via the p53/NLRP3 axis. Targeting KAT8 with MG149 represents a promising therapeutic strategy to mitigate inflammation and oxidative injury in ALI.

Bombyx mori nucleopolyhedrovirus (BmNPV) infection is a critical disease in silkworms (Bombyx mori), yet the molecular mechanism underlying the defense of Bombyx mori against BmNPV infection remains elusive. The histone acetyltransferase MOF plays a crucial role in cellular stress response and apoptosis. Nevertheless, its function in Bombyx mori is yet to be fully elucidated. Here, we demonstrated that BmMOF positively regulates the resistance of silkworm BmN cells to BmNPV by targeting a Bombyx mori homolog of the apoptosis-inducing factor Bmp53. Overexpression of BmMOF led to the suppression of BmNPV proliferation and the enhancement of cellular antiviral responses, conversely, RNA interference targeting BmMOF promoted viral proliferation, resulting in an opposite effect. Additionally, the application of the acetyltransferase inhibitor MG149 and the mutated BmMOF acetyltransferase active site K257R revealed that BmMOF is capable of acetylating H4K16 in BmN cells, and its acetylation function plays a crucial role in inhibiting virus proliferation. Further analyses showed that BmMOF interacted with Bmp53 and catalyzes its acetylation, thereby inducing the apoptosis-mediated antiviral immune response in BmN cells upon infection with BmNPV. These findings provided a new molecular target for antiviral immunity and information for comprehending the mechanism of host-virus interaction in silkworms.