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首页> 外文期刊>The European Journal of Neuroscience >Programmed cell death in the neurulating embryo is prevented by the chaperone heat shock cognate 70.
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Programmed cell death in the neurulating embryo is prevented by the chaperone heat shock cognate 70.

机译:伴侣热休克同源70防止了胚胎中程序性细胞死亡。

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摘要

Neuronal cell death is a genuine developmental process, with precise regulation and defined roles. In striking contrast, characterization of cell death that occurs at early stages of neural development is very limited. We previously showed that embryonic proinsulin increases the level of the chaperone heat shock cognate 70 (Hsc70) and reduces the incidence of apoptosis in the neurulating chick embryo [de la Rosa, et al. (1998), Proc. Natl. Acad. Sci. USA, 95, 9950]. We now demonstrate that Hsc70 is directly involved in cell survival during neurulation, as specific downregulation of endogenous Hsc70 by antisense oligodeoxynucleotide interference provoked an increase in apoptosis both in vitro and in ovo. In parallel, activation of caspase-3 was increased after hsc70 antisense oligodeoxynucleotide treatment. Dead cells were located mostly in the developing nervous system, distributed in areas where the incidence of cell death was high. These areas coincided both in vivo and under different death-inducing conditions, including antisense interference and growth factor deprivation. Hsc70 immunostaining was strong in at least some areas of high cell death. Apoptotic cells within these areas presented undetectable Hsc70 levels, however, suggesting that this protein acts as an intrinsic protector of neuroepithelial and neural precursor cells.
机译:神经元细胞死亡是一个真正的发育过程,具有精确的调控和明确的作用。与之形成鲜明对比的是,在神经发育的早期阶段发生的细胞死亡的特征非常有限。先前我们发现胚胎胰岛素原增加了伴侣热休克同源蛋白70(Hsc70)的水平,并减少了有营养的雏鸡胚胎中细胞凋亡的发生率[de Rosa,et al。 (1998),过程。 Natl。学院科学美国,95,9950]。我们现在证明,Hsc70直接参与神经元的细胞存活,因为通过反义寡聚脱氧核苷酸干扰对内源性Hsc70的特异性下调在体外和卵内引起了细胞凋亡的增加。平行地,在hsc70反义寡脱氧核苷酸处理后,caspase-3的活化增加。死细胞主要位于发育中的神经系统中,分布在细胞死亡发生率高的区域。这些区域在体内和在不同的诱导死亡条件下均重合,包括反义干扰和生长因子剥夺。 Hsc70免疫染色在高细胞死亡的至少某些区域很强。这些区域内的凋亡细胞呈现出无法检测到的Hsc70水平,然而,表明该蛋白可作为神经上皮和神经前体细胞的固有保护物。

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