脂筏破坏可防止白血病细胞系中2-氯-2'-脱氧腺苷（克拉屈滨）诱导的细胞凋亡。

Lipid raft disruption prevents apoptosis induced by 2-chloro-2'-deoxyadenosine (Cladribine) in leukemia cell lines.

作者信息

Takahashi Eriko, Inanami Osamu, Ohta Toshio, Matsuda Akira, Kuwabara Mikinori

机构信息

Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18 jo Nishi 9 chome, Sapporo, Japan.

出版信息

Leuk Res. 2006 Dec;30(12):1555-61. doi: 10.1016/j.leukres.2006.04.008. Epub 2006 May 26.

DOI:10.1016/j.leukres.2006.04.008

PMID:16730061

Abstract

To clarify the role of lipid rafts in 2-chloro-2'-deoxyadenosine (2CdA; Cladribine)-induced apoptosis, the effects of disruption of lipid rafts by methyl-beta-cyclodextrin (MbetaCD) and filipin on 2CdA-induced apoptosis were investigated in four human acute lymphoblastic leukemia (ALL) cell lines comprised of T cells (MOLT-4, Jurkat) and B cells (NALM, BALL-1). The disruption of lipid rafts significantly inhibited 2CdA-induced apoptosis, indicating the crucial role of lipid rafts in the induction of apoptosis in leukemia cells. These reagents significantly inhibited 2CdA-induced elevation of the intracellular calcium concentration (Ca(2+)) in MOLT-4 cells, and 2CdA-induced apoptosis was partly inhibited by the Ca(2+) chelators BAPTA-AM and EGTA, and the L-type Ca(2+) channel blocker nifedipine. On the other hand, they had no effects on the cellular uptake of 2CdA. These results indicated that lipid rafts partly contributed to 2CdA-induced apoptosis by regulating Ca(2+) influx via the plasma membrane.

摘要

为阐明脂筏在2-氯-2'-脱氧腺苷（2CdA；克拉屈滨）诱导的细胞凋亡中的作用，研究了用甲基-β-环糊精（MβCD）和制霉菌素破坏脂筏对4种人急性淋巴细胞白血病（ALL）细胞系（包括T细胞系（MOLT-4、Jurkat）和B细胞系（NALM、BALL-1））中2CdA诱导的细胞凋亡的影响。脂筏的破坏显著抑制了2CdA诱导的细胞凋亡，表明脂筏在白血病细胞凋亡诱导中起关键作用。这些试剂显著抑制了2CdA诱导的MOLT-4细胞内钙浓度（[Ca(2+)]i）的升高，并且2CdA诱导的细胞凋亡被Ca(2+)螯合剂BAPTA-AM和EGTA以及L型Ca(2+)通道阻滞剂硝苯地平部分抑制。另一方面，它们对2CdA的细胞摄取没有影响。这些结果表明，脂筏通过调节质膜的Ca(2+)内流部分促进了2CdA诱导的细胞凋亡。