Sulforaphane diminishes moonlighting of pyruvate kinase M2 and interleukin 1β expression in M1 (LPS) macrophages.
Sulforaphane diminishes moonlighting of pyruvate kinase M2 and interleukin 1β expression in M1 (LPS) macrophages.
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DOI：
10.3389/fimmu.2022.935692
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
由Toll样受体4激动剂脂多糖（LPS）激活的小鼠巨噬细胞通过诱导促炎标记蛋白并改变其能量代谢以增加有氧糖酵解和减少呼吸而转化为M1型。我们在这里发现，脂肪族异硫氰酸酯萝卜硫素（Sfn）减少M1标记物（IL-1β，IL-6，TNF-α，iNOS，NO和ROS）的表达，并导致高能量的细胞，其特征是高糖酵解和高呼吸活性，通过细胞外流量分析评估。聚焦于M1（LPS/Sfn）巨噬细胞中高糖酵解活性和低IL-1β表达之间的潜在联系，我们揭示了Sfn阻碍M1巨噬细胞中丙酮酸激酶M2（PKM 2）的兼职功能。Sfn限制PKM 2的单/二聚化和核驻留，伴随着降低的HIF-1α水平、Stat 3在酪氨酸705处的磷酸化和IL-1β表达，同时保持高水平的具有高糖酵解酶活性的胞质PKM 2四聚体。Sfn阻止LPS刺激的巨噬细胞中PKM 2的谷胱甘肽化，这可能是PKM 2四聚体损失减少的原因。总体而言，我们发现PKM 2是Sfn抗炎活性特征中一个新的受影响的枢纽。
Murine macrophages activated by the Toll-like receptor 4 agonist lipopolysaccharide (LPS) polarize to the M1 type by inducing proinflammatory marker proteins and changing their energy metabolism to increased aerobic glycolysis and reduced respiration. We here show that the aliphatic isothiocyanate sulforaphane (Sfn) diminishes M1 marker expression (IL-1β, IL-6, TNF-α, iNOS, NO, and ROS) and leads to highly energetic cells characterized by both high glycolytic and high respiratory activity as assessed by extracellular flux analysis. Focusing on a potential connection between high glycolytic activity and low IL-1β expression in M1 (LPS/Sfn) macrophages, we reveal that Sfn impedes the moonlighting function of pyruvate kinase M2 (PKM2) in M1 macrophages. Sfn limits mono/dimerization and nuclear residence of PKM2 accompanied by reduced HIF-1α levels, Stat3 phosphorylation at tyrosine 705, and IL-1β expression while preserving high levels of cytosolic PKM2 tetramer with high glycolytic enzyme activity. Sfn prevents glutathionylation of PKM2 in LPS-stimulated macrophages which may account for the reduced loss of PKM2 tetramer. Overall, we uncover PKM2 as a novel affected hub within the anti-inflammatory activity profile of Sfn.
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影响因子：
14.9
作者：
Kuosmanen SM;Kansanen E;Kaikkonen MU;Sihvola V;Pulkkinen K;Jyrkkänen HK;Tuoresmäki P;Hartikainen J;Hippeläinen M;Kokki H;Tavi P;Heikkinen S;Levonen AL
通讯作者：
Levonen AL
影响因子：
3.1
作者：
Mak, Lora;Liggi, Sonia;Kirchmair, Johannes
通讯作者：
Kirchmair, Johannes
DOI：
10.3390/ph7090913
发表时间：
2014-09-04
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
--
作者：
Grabacka MM;Gawin M;Pierzchalska M
通讯作者：
Pierzchalska M
影响因子：
9.3
作者：
Hernandez-Rabaza V;Cabrera-Pastor A;Taoro-Gonzalez L;Gonzalez-Usano A;Agusti A;Balzano T;Llansola M;Felipo V
通讯作者：
Felipo V
影响因子：
8.8
作者：
Bae S;Park PSU;Lee Y;Mun SH;Giannopoulou E;Fujii T;Lee KP;Violante SN;Cross JR;Park-Min KH
通讯作者：
Park-Min KH