Shatrov V A, Lehmann V, Chouaib S
CJF 94-11 INSERM Cytokines et Immunitè Antitumorale, Institut Gustave-Roussy, Villejuif, France.
Biochem Biophys Res Commun. 1997 May 8;234(1):121-4. doi: 10.1006/bbrc.1997.6598.
Sphingosine-1-phosphate (SPP), a metabolite of sphingolipids, has been implicated as a second messenger in cell growth regulation and signal transduction via calcium mobilization from internal stores. This study shows that SPP mobilizes intracellular calcium in U937 cells and demonstrates for the first time the ability of SPP to activate the transcription factor NF-kappa B in these cells. Furthermore, calcium release from the internal stores by thapsigargin (TG), an inhibitor of the endoplasmic reticulum Ca2+ pump, was associated with activation of NF-kappa B. Moreover, we have shown that while an intracellular calcium chelator BAPTA/AM was able to inhibit both SPP- and TG-induced NF-kappa B activation, it had no effect on TNF-induced NF-kappa B activation. In addition, SPP-induced NF-kappa B activation was blocked both by cyclosporin A, known to inhibit calcineurin phosphatase activity, and by the antioxidant butylated hydroxyanisole. These observations suggest that intracellular calcium mobilization is required for SPP-induced NF-kappa B activation, which may involve calcineurin- and redox-dependent mechanisms.
鞘氨醇-1-磷酸（SPP）是鞘脂的一种代谢产物，被认为是细胞生长调节和通过从细胞内储存库动员钙进行信号转导过程中的第二信使。本研究表明，SPP可动员U937细胞内的钙，并首次证明SPP在这些细胞中激活转录因子NF-κB的能力。此外，内质网Ca2+泵抑制剂毒胡萝卜素（TG）引起的细胞内储存库钙释放与NF-κB的激活有关。而且，我们已经表明，虽然细胞内钙螯合剂BAPTA/AM能够抑制SPP和TG诱导的NF-κB激活，但对TNF诱导的NF-κB激活没有影响。此外，已知抑制钙调神经磷酸酶活性的环孢素A和抗氧化剂丁基羟基茴香醚均可阻断SPP诱导的NF-κB激活。这些观察结果表明，细胞内钙动员是SPP诱导NF-κB激活所必需的，这可能涉及钙调神经磷酸酶和氧化还原依赖性机制。
