Simizu Siro, Teruya Takayuki, Nogawa Toshihiko, Aono Harumi, Ueki Masashi, Uramoto Masakazu, Kobayashi Yuichi, Osada Hiroyuki
Antibiotics Laboratory and Chemical Biology Department, Advanced Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Biochem Biophys Res Commun. 2009 Jun 12;383(4):406-10. doi: 10.1016/j.bbrc.2009.04.014. Epub 2009 Apr 11.
During the screening for novel differentiation inducers, we found that a culture broth of Streptomyces sp. HK-803 induced myeloid differentiation of HL-60 cells. The active substance was identified as deamino-hydroxy-phoslactomycin B (HPLM) by mass spectrometry, and synthesized HPLM also induced the differentiation of HL-60 cells. HPLM showed greater inhibition of protein phosphatase 2A (PP2A) activity than phoslactomycin B (PLMB); however, PLMB and okadaic acid did not induce differentiation. Moreover, treatment with ATRA and 1alpha, 25(OH)2D3 induced retinoic acid receptor-beta and 1alpha, 25(OH)2D3 24-hydroxylase, respectively, whereas HPLM did not, suggesting that HPLM is a novel differentiation inducer.
在筛选新型分化诱导剂的过程中，我们发现链霉菌属HK - 803的培养液可诱导HL - 60细胞发生髓系分化。通过质谱分析将活性物质鉴定为脱氨基 - 羟基 - 磷雷帕霉素B（HPLM），并且合成的HPLM也能诱导HL - 60细胞分化。与雷帕霉素B（PLMB）相比，HPLM对蛋白磷酸酶2A（PP2A）活性的抑制作用更强；然而，PLMB和冈田酸并未诱导分化。此外，全反式维甲酸（ATRA）和1α，25 - 二羟基维生素D3 [1α，25(OH)2D3]处理分别诱导了维甲酸受体β和1α，25 - 二羟基维生素D3 24 - 羟化酶，而HPLM则没有，这表明HPLM是一种新型分化诱导剂。
