Inhibition of arachidonic acid release and cytosolic phospholipase A2 alpha activity by D-erythro-sphingosine.

Inhibition of arachidonic acid release and cytosolic phospholipase A2 alpha activity by D-erythro-sphingosine.
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D-赤型鞘氨醇抑制花生四烯酸释放和胞质磷脂酶 A2 α 活性。

DOI:
10.1016/j.ejphar.2003.10.053
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发表时间:
2004
影响因子:
5
通讯作者:
T. Murayama
T. Murayama
中科院分区:
医学2区
文献类型:
--
作者:
Hiroyuki Nakamura;Testuya Hirabayashi;Akiyoshi Someya;Masaya Shimizu;T. Murayama

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鞘磷脂代谢产物如1-磷酸鞘氨醇(S1P)和神经酰胺可介导许多细胞事件,包括细胞凋亡、应激反应和生长停滞。尽管神经酰胺能刺激几个细胞的花生四烯酸代谢,但鞘氨醇及其内源性类似物的作用尚未确定。我们研究了d-红血鞘氨醇及其代谢产物对这两种细胞花生四烯酸释放和胞浆磷脂酶A2α活性的影响。C2-神经酰胺(N-乙酰-d-红神经鞘氨醇,100μM)单独刺激预先标记的PC12细胞和L929细胞释放[~3H]花生四烯酸,并增强离子霉素诱导的释放。相反,外源性的D-红血球鞘氨醇以浓度依赖的方式抑制这两种细胞系的反应。D-赤霉醇、D-赤霉醇-N,N-二甲基鞘氨醇(d-Redthro-DMS)和d-赤霉醇二氢鞘氨醇(d-Redthro-DHS)可显著抑制由Mastoparan-刺激的花生四烯酸释放,但对Na3VO4-的抑制作用不明显。D-红血球-S_1P和dl-苏氨酸-DHS对上述反应无影响。C2-神经酰胺(20αM)可促进PC12细胞前列腺素F2μ的产生,10μM可抑制前列腺素F2 DNA的产生。体外实验表明,D-红神经鞘氨醇、D-DMS和D-DHS可直接抑制胞浆磷脂酶A2α活性。这些发现表明神经酰胺和神经鞘氨醇的D-红血球类似物对磷脂酶A2的活性有相反的影响,从而调节细胞释放花生四烯酸。
Sphingolipid metabolites such as sphingosine 1-phosphate (S1P) and ceramide can mediate many cellular events including apoptosis, stress responses and growth arrest. Although ceramide stimulates arachidonic acid metabolism in several cells, the effects of sphingosine and its endogenous analogs have not been established. We investigated the effects of d-erythro-sphingosine and its metabolites on arachidonic acid release in the two cells and on the activity of cytosolic phospholipase A2α. C2-Ceramide (N-acetyl-d-erythro-sphingosine, 100 μM) alone stimulated [3H]arachidonic acid release and enhanced the ionomycin-induced release from the prelabeled PC12 cells and L929 cells. In contrast, exogenous addition of d-erythro-sphingosine inhibited the responses in a concentration-dependent manner in the two cell lines. d-erythro-sphingosine, d-erythro-N,N-dimethylsphingosine (d-erythro-DMS) and d-erythro-dihydrosphingosine (d-erythro-DHS) significantly inhibited mastoparan-, but not Na3VO4-, stimulated arachidonic acid release in PC12 cells. d-erythro-S1P and dl-threo-DHS showed no effect on the responses. Production of prostaglandin F2αwas also enhanced by C2-ceramide (20 μM) and suppressed by d-erythro-sphingosine (10 μM) in PC12 cells. An in vitro study revealed that d-erythro-sphingosine, d-erythro-DMS and d-erythro-DHS directly inhibited cytosolic phospholipase A2α activity. These findings suggest that ceramide and d-erythro-analogs of sphingosine have opposite effects on phospholipase A2activity and thus regulate arachidonic acid release from cells.
DOI: 10.1074/jbc.273.37.23722
发表时间: 1998-09-11
影响因子: 4.8
作者:
Kohama, T;Olivera, A;Spiegel, S
通讯作者: Spiegel, S
DOI: 10.1046/j.1471-4159.2001.00164.x
发表时间: 2001-03-01
影响因子: 4.7
作者:
Edsall, LC;Cuvillier, O;Milstien, S
通讯作者: Milstien, S
DOI: 10.1074/jbc.m304816200
发表时间: 2003-10-03
影响因子: 4.8
作者:
Pettus, BJ;Bielawska, A;Chalfant, CE
通讯作者: Chalfant, CE
DOI: 10.1021/bi980744d
发表时间: 1998-09-15
期刊: BIOCHEMISTRY
影响因子: 2.9
作者:
Edsall, LC;Van Brocklyn, JR;Spiegel, S
通讯作者: Spiegel, S
花生四烯酸-磷脂重塑与细胞凋亡的关系。
DOI: 10.1021/bi9530245
发表时间: 1996
期刊: Biochemistry.
影响因子: --
作者:
Surette,ME;Winkler,JD;Fonteh,AN;Chilton,FH
通讯作者: Chilton,FH