Feb 25, 2020 · We show that an Hdac7-Pkm2 complex acts as an immunometabolism signaling hub, whereby Pkm2 deacetylation at lysine 433 licenses its proinflammatory functions. Disrupting this complex suppresses inflammatory responses in vitro and in vivo. Class IIa HDACs are thus pivotal intermediates connecting TLR-inducible glycolysis to inflammation via Pkm2.

Feb 25, 2020 · We show that an Hdac7-Pkm2 complex acts as an immunometabolism signaling hub, whereby Pkm2 deacetylation at lysine 433 licenses its proinflammatory functions. Disrupting this complex suppresses inflammatory responses in vitro and in vivo.

In summary, HDAC7 enzymatic activity is required for its capacity to promote bacterial phagocytosis and killing by macrophages, glucose uptake is required for the response, and the mechanism is distinct to the HDAC7-PKM2-IL-1β axis.

We show that an Hdac7-Pkm2 complex acts as an immunometabolism signaling hub, whereby Pkm2 deacetylation at lysine 433 licenses its proinflamma-tory functions. Disrupting this complex suppresses inflammatory responses in vitro and in vivo. Class IIa HDACs are thus pivotal intermediates connect-ing TLR-inducible glycolysis to inflammation via ...

Mar 18, 2022 · The mechanism involves Hdac7-mediated deacetylation of the glycolytic enzyme Pkm2, enabling activation of the transcription factor Hif-1α and initiation of inflammatory gene expression. Hdac7 also promotes TLR-inducible glycolysis [ [ 26 , 29 ] ], a metabolic response increasingly linked to inflammation [ [ 75 ] ].

Apart from its involvement in this inflammatory pathway, the proteomic screen that revealed an association between HDAC7 and PKM2 also identified the pentose phosphate pathway (PPP) enzyme 6-phosphogluconate dehydrogenase (6PGD) as a candidate HDAC7-interacting partner .

Jun 24, 2024 · Class IIa histone deacetylase HDAC7 mediates the deacetylation of PKM2 at Lys433 to aggravate its proinflammatory property (Das Gupta et al., 2020). Sirt3 mediates the deacetylation of PKM2 at Lys433 in A549 cells, which process significantly alleviates apoptosis against lung ischemia/reperfusion injury ( Zhao et al., 2022 ).

Nov 23, 2021 · We previously showed that expression of Hdac7, a class IIa HDAC, is elevated in inflammatory macrophages over other macrophage populations. 17 Moreover, Hdac7 interacts with Pkm2 to drive Hif-1α-dependent Il1b expression in murine macrophages, thus providing a potential mechanistic link between TLR-inducible metabolic and inflammatory ...

A proteomic screen identified the glycolytic enzyme pyruvate kinase M isoform 2 (Pkm2) as a partner of proinflammatory Hdac7 in murine macrophages. Myeloid-specific Hdac7 overexpression in transgenic mice amplifies lipopolysaccharide (LPS)-inducible lactate and promotes a glycolysis-associated inflammatory signature.

hdac7 通过使 k433 上的糖酵解酶 pkm2 去乙酰化来促进 lps 诱导的炎症反应。在这里，作者发现 dasa 可以拮抗 pkm2 和 hdac7 的促炎功能，但不会影响 hdac7 的抗菌功能。