Thyroid hormone regulation of apoptosis induced by retinoic acid in promyeloleukemic HL-60 cells: Studies with retinoic acid receptor-specific and retinoid x receptor-specific ligands
Thyroid hormone regulation of apoptosis induced by retinoic acid in promyeloleukemic HL-60 cells: Studies with retinoic acid receptor-specific and retinoid x receptor-specific ligands
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DOI：
10.1089/thy.2000.10.1023
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发表时间：
2000-12-01
期刊：
影响因子：
6.6
通讯作者：
Hashizume, K
中科院分区：
文献类型：
--
作者：
Hara, M;Suzuki, S;Hashizume, K
3,5,3'-三碘- l-甲状腺原氨酸（T-3）在全反式维甲酸诱导的早幼粒细胞白血病HL-60细胞分化过程中增强凋亡。我们在本研究中检测了在HL-60细胞分化过程中是否存在类视黄酮受体特异性甲状腺激素作用。我们使用了两种不同的类视黄醇受体激动剂。T-3可增强视黄酸受体（RAR）特异性激动剂Am80诱导的G(1)阻滞，但对类视黄酸受体（RXR）特异性激动剂HX600诱导的G(1)阻滞无影响。Am80单独诱导细胞凋亡，T-3促进细胞凋亡。虽然单独HX600不能增加细胞凋亡比例，但T-3能使化合物诱导细胞凋亡。T-3可增强am80诱导的CD11b（分化标志物）的表达，而T-3或HX600或两者均不影响CD11b的表达。T-3不会改变bcl-2家族各种成员mrna的数量。而T-3可增强am80诱导的bfl-1表达，抑制bcl-2。相比之下，在HX600存在的情况下，T-3不改变bfl-1和bcl-2的表达。我们的观察结果表明，T-3与rxr特异性配体在细胞凋亡调节中的协同作用不同于与RAR配体的协同作用，甲状腺激素可能可作为急性白血病的化疗药物。
3,5,3'-Triiodo-L-thyronine (T-3) potentiates apoptosis during the all-trans-retinoic acid-induced differentiation of promyeloleukemic HL-60 cells. We examined whether the retinoid receptor-specific thyroid hormone action is present during differentiation of HL-60 cells in this study. We used two distinct retinoid receptor agonists. T-3 potentiates G(1) arrest induced by Am80, a retinoic acid receptor (RAR)-specific agonist, but had no effect on G(1) arrest induced by HX600, a retinoid x receptor (RXR)-specific agonist. Am80 alone induces the apoptosis, and T-3 enhances it. Although HX600 alone fails to increase the apoptotic fraction, T-3 enables the compounds to induce apoptosis. Am80-induced expression of CD11b, a marker for the differentiation, is enhanced by T-3 However, T-3 or HX600 or both do not affect the expression of CD11b. T-3 does not alter the amount of mRNAs of various members of the bcl-2 family. T-3, however, enhances the Am80-induced expression of bfl-1 and suppression of bcl-2. In contrast, T-3 does not alter either bfl-1 and bcl-2 expression in the presence of HX600. Our observations suggest that cooperative action of T-3 With an RXR-specific ligand is different from that with an RAR ligand in cellular apoptotic regulation and that thyroid hormone may be available as a chemotherapeutic agent in acute leukemia.