Delta opioid peptide DADLE and naltrexone cause cell cycle arrest and differentiation in a CNS neural progenitor cell line.

Delta opioid peptide DADLE and naltrexone cause cell cycle arrest and differentiation in a CNS neural progenitor cell line.
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DOI:
10.1002/syn.20727
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发表时间:
2010-04
期刊:
影响因子:
2.3
通讯作者:
Su, Tsung-Ping
Su, Tsung-Ping
中科院分区:
医学4区
文献类型:
--
作者:
Tsai, Shang-Yi;Lee, Chung-Ting;Hayashi, Teruo;Freed, William J.;Su, Tsung-Ping

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阿片类药物已被证明通过影响各种类型神经细胞的增殖和分化在CNS发育中发挥重要作用。本研究观察了稳定的δ阿片肽[d-Ala(2),d-Leu(5)]-脑啡肽(DADLE)对大鼠中脑神经前体细胞系AF 5增殖和分化的影响。DADLE(1 pM、0.1 nM或10 nM)对AF 5细胞产生显著的生长抑制。阿片类药物拮抗剂纳洛酮在0.1 nM时也引起相同细胞的生长抑制。当DADLE和纳洛酮同时加入到AF 5细胞中时,所产生的生长抑制明显是加和的。如阴性TUNEL染色所证明的,单独的DADLE或DADLE与纳洛酮的组合不引起细胞凋亡。细胞周期进程分析表明,DADLE(0.1 nM)和纳洛酮(0.1 nM)均导致AF 5细胞周期进程在G1检查点停滞。神经元标记物表明,DADLE或纳洛酮处理的AF 5细胞倾向于分化更多时,与对照组相比。结果表明DADLE和纳洛酮对CNS神经祖细胞系的细胞周期阻滞和分化的非阿片样作用。结果还表明DADLE和/或纳曲酮在干细胞研究中的一些潜在用途。
Opioids have been demonstrated to play an important role in CNS development by affecting proliferation and differentiation in various types of neural cells. This study examined the effect of a stable delta opioid peptide [d-Ala(2), d-Leu(5)]-enkephalin (DADLE) on proliferation and differentiation in an AF5 CNS neural progenitor cell line derived from rat mesencephalic cells. DADLE (1 pM, 0.1 nM, or 10 nM) caused a significant growth inhibition on AF5 cells. The opioid antagonist naltrexone at 0.1 nM also caused growth inhibition in the same cells. When DADLE and naltrexone were both added to the AF5 cells, the resultant growth inhibition was apparently additive. DADLE alone or DADLE in combination with naltrexone did not cause apoptosis as evidenced by negative TUNEL staining. The cell-cycle progression analysis indicated that both DADLE (0.1 nM) and naltrexone (0.1 nM) caused an arrest of AF5 cell cycle progression at the G1 checkpoint. Neuronal marker indicated that DADLE- or naltrexone-treated AF5 cells tend to differentiate more when compared to controls. Results demonstrate the nonopioid action of both DADLE and naltrexone on cell cycle arrest and differentiation in a CNS neural progenitor cell line. Results also suggest some potential utilization of DADLE and/or naltrexone in stem cell research.
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发表时间: 2002-01-01
期刊: SYNAPSE
影响因子: 2.3
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期刊: CANCER LETTERS
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