Nuclear Sphingosine-1-phosphate Lyase Generated ∆2-hexadecenal is A Regulator of HDAC Activity and Chromatin Remodeling in Lung Epithelial Cells.
Nuclear Sphingosine-1-phosphate Lyase Generated ∆2-hexadecenal is A Regulator of HDAC Activity and Chromatin Remodeling in Lung Epithelial Cells.
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核鞘氨醇-1-磷酸裂解酶产生的β 2-十六烯醛是肺上皮细胞HDAC活性和染色质重塑的调节剂。
DOI：
10.1007/s12013-021-01005-9
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发表时间：
2021-09
影响因子：
2.6
通讯作者：
Natarajan V
中科院分区：
文献类型：
--
作者：
Ebenezer DL;Ramchandran R;Fu P;Mangio LA;Suryadevara V;Ha AW;Berdyshev E;Van Veldhoven PP;Kron SJ;Schumacher F;Kleuser B;Natarajan V
鞘氨醇-1-磷酸（S1P）是一种生物活性脂质介质，由鞘氨醇激酶（SPHKs） 1和2产生，并在哺乳动物细胞中被S1P裂解酶（S1PL）代谢为Δ2-hexadecenal （Δ2-HDE）和乙醇胺磷酸。我们最近证明了暴露于铜绿假单胞菌的肺上皮细胞的细胞核中SPHK2的活化和S1P的产生。在这里，我们研究了S1PL的核定位以及S1P在细胞核中产生的Δ2-HDE作为组蛋白去乙酰化酶（HDAC）活性和组蛋白乙酰化的调节剂的作用。从MLE-12细胞分离的核组分电镜图显示细胞核没有ER污染，并且在原代肺支气管上皮细胞和肺泡上皮MLE-12细胞分离的核组分中检测到S1PL活性。铜绿假单胞菌介导的核Δ2-HDE生成和H3/H4组蛋白乙酰化被S1PL抑制剂在MLE-12细胞和人支气管上皮细胞中减弱。在体外，肺上皮细胞核制剂中添加外源Δ2-HDE （100-10,000 nM）可抑制HDAC1/2活性，并增加组蛋白H3和H4的乙酰化，而相似浓度的S1P未表现出显著变化。此外，通过LC-MS/MS检测，Δ2-HDE与rHDAC1孵育产生5种不同的氨基酸加合物；主要的加合物是Δ2-HDE与HDAC1的赖氨酸残基。总之，这些数据表明核s1pl衍生的Δ2-HDE在肺上皮细胞中HDAC活性的修饰、组蛋白乙酰化和染色质重塑中的重要作用。
Sphingosine-1-phosphate (S1P), a bioactive lipid mediator, is generated from sphingosine by sphingosine kinases (SPHKs) 1 and 2 and is metabolized to Δ2-hexadecenal (Δ2-HDE) and ethanolamine phosphate by S1P lyase (S1PL) in mammalian cells. We have recently demonstrated the activation of nuclear SPHK2 and the generation of S1P in the nucleus of lung epithelial cells exposed to Pseudomonas aeruginosa. Here, we have investigated the nuclear localization of S1PL and the role of Δ2-HDE generated from S1P in the nucleus as a modulator of histone deacetylase (HDAC) activity and histone acetylation. Electron micrographs of the nuclear fractions isolated from MLE-12 cells showed nuclei free of ER contamination, and S1PL activity was detected in nuclear fractions isolated from primary lung bronchial epithelial cells and alveolar epithelial MLE-12 cells. Pseudomonas aeruginosa-mediated nuclear Δ2-HDE generation, and H3/H4 histone acetylation was attenuated by S1PL inhibitors in MLE-12 cells and human bronchial epithelial cells. In vitro, the addition of exogenous Δ2-HDE (100–10,000 nM) to lung epithelial cell nuclear preparations inhibited HDAC1/2 activity, and increased acetylation of Histone H3 and H4, whereas similar concentrations of S1P did not show a significant change. In addition, incubation of Δ2-HDE with rHDAC1 generated five different amino acid adducts as detected by LC-MS/MS; the predominant adduct being Δ2-HDE with lysine residues of HDAC1. Together, these data show an important role for the nuclear S1PL-derived Δ2-HDE in the modification of HDAC activity, histone acetylation, and chromatin remodeling in lung epithelial cells.
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鞘氨醇激酶和1-磷酸盐受体：心血管系统中的信号传导和作用。
影响因子：
5.6
作者：
Cannavo A;Liccardo D;Komici K;Corbi G;de Lucia C;Femminella GD;Elia A;Bencivenga L;Ferrara N;Koch WJ;Paolocci N;Rengo G
通讯作者：
Rengo G
影响因子：
4.1
作者：
LoPachin, Richard M.;Gavin, Terrence;Petersen, Dennis R.;Barber, David S.
通讯作者：
Barber, David S.
DOI：
10.1126/science.1176709
发表时间：
2009-09-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hait NC;Allegood J;Maceyka M;Strub GM;Harikumar KB;Singh SK;Luo C;Marmorstein R;Kordula T;Milstien S;Spiegel S
通讯作者：
Spiegel S
影响因子：
2.9
作者：
Berdyshev EV;Goya J;Gorshkova I;Prestwich GD;Byun HS;Bittman R;Natarajan V
通讯作者：
Natarajan V
影响因子：
4.8
作者：
Kohama, T;Olivera, A;Spiegel, S
通讯作者：
Spiegel, S