The constitutive heat shock protein-70 is required for optimal expression of myelin basic protein during differentiation of oligodendrocytes
The constitutive heat shock protein-70 is required for optimal expression of myelin basic protein during differentiation of oligodendrocytes
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DOI：
10.1023/a:1022473904335
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发表时间：
1998-03-01
影响因子：
4.4
通讯作者：
Farooq, M
中科院分区：
文献类型：
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作者：
Aquino, DA;Peng, D;Farooq, M
为了进一步阐明组成性热休克蛋白-70（HSC 70）作为髓鞘碱性蛋白（MBP）合成的伴侣的作用，在MBP表达之前，通过用HSC 70特异性的反义寡核苷酸转染或通过暴露于低水平的槲皮素（已知降低HSC 70合成的生物素）来降低少突胶质细胞前体细胞中的HSC 70含量。当这些细胞在体外分化时，反义处理使HSC 70水平降低至对照的66%。同时，急剧诱导导致应激诱导的热休克蛋白70（HSP 70）。另外两种应激蛋白的水平也增加了，即25-kDa热休克蛋白（HSP 25）和78-kDa葡萄糖调节蛋白（GRP78）。MBP的合成在正常的时间过程中进行，但只有50%的控制值。随着HSC 70含量恢复正常，MBP合成也恢复到正常水平。槲皮素降低HSC 70的表达，甚至比转染更大的程度，并阻止HSP 70的诱导。相反，反义处理的细胞，MBP合成基本上被阻止在槲皮素处理的细胞，即使HSP 25和GRP78的水平增加。综上所述，这些观察结果（a）表明HSP 70部分补偿了HSC 70对新生MBP的伴侣作用的减少（HSC 70和HSP 70密切相关并且执行相似的功能）;（B）排除了HSP 25和GRP78参与MBP合成;以及（c）强调了对MBP最佳合成的HSC 70的需求。
To further elucidate the role of the constitutive hear shock protein-70 (HSC70) as a chaperone for the synthesis of myelin basic protein (MBP), HSC70 content was decreased in oligodendrocyte precursor cells prior to MBP expression either by transfection with an antisense oligonucleotide specific for HSC70, or by exposure to low levels of quercetin, a bioflavonoid known to decrease synthesis of HSC70. As these cells underwent differentiation in vitro, antisense treatment decreased HSC70 levels to 66% of controls. At the same time, a sharp induction resulted in the stress-inducible heat shock protein-70 (HSP70). Levels of two other stress proteins increased as well, namely, the 25-kDa heat shock protein (HSP25) and the 78-kDa glucose regulated protein (GRP78). MBP synthesis proceeded over a normal time course, but al only 50% of control values. As HSC70 content returned to normal, MBP synthesis was also restored to normal levels. Quercetin reduced the expression of HSC70 to an even greater extent than transfection, and prevented the induction of HSP70. In contrast to antisense-treated cells, MBP synthesis was essentially blocked in quercetin-treated cells even though levels of HSP25 and GRP78 increased. Taken together, these observations (a) indicate that HSP70 partially compensates for decreased chaperoning of nascent MBP by HSC70 (HSC70 and HSP70 are closely related and perform similar functions); (b) preclude the involvement of HSP25 and GRP78 in MBP synthesis; and (c) emphasize the requirement of HSC70 for optimal synthesis of MBP.