The role of 2′-5′ oligoadenylate-activated ribonuclease L in apoptosis
The role of 2′-5′ oligoadenylate-activated ribonuclease L in apoptosis
复制标题
DOI：
10.1038/sj.cdd.4400352
复制
发表时间：
1998-04-01
影响因子：
12.4
通讯作者：
Youle, RJ
中科院分区：
文献类型：
--
作者：
Castelli, JC;Hassel, BA;Youle, RJ
病毒感染细胞的凋亡似乎是限制病毒感染的一种防御策略。干扰素还可以通过诱导由2‘-5’寡腺苷合成酶(GAS)和核糖核酸酶L组成的2-5A系统来赋予病毒耐药性，因为核糖核酸在核糖核酸酶L激活时和在细胞凋亡过程中被降解，并且这两个过程都具有抗病毒功能，我们研究了核糖核酸酶L在细胞死亡中可能发挥的作用。抑制核糖核酸酶L活性可阻断星孢菌素诱导的NIH3T3细胞和SV40转化的BALB/c细胞的凋亡，并且表达失活核糖核酸酶L的K562细胞对谷胱甘肽水平降低所诱导的细胞凋亡具有更强的抵抗力。过氧化氢诱导的NIH3T3细胞死亡不是通过细胞凋亡发生的，也不依赖于活性的核糖核酸酶L。在缺乏核糖核酸酶L活性的情况下，Bcl2家族的凋亡调节蛋白的表达水平没有变化，核糖核酸酶L是细胞死亡的某些途径所必需的，可能有助于介导病毒诱导的细胞凋亡。
Apoptosis of viral infected cells appears to be one defense strategy to limit viral infection. Interferon can also confer viral resistance by the induction of the 2-5A system com prised of 2'-5' oligoadenylate synthetase (GAS), and RNase L., Since rRNA is degraded upon activation of RNase L and during apoptosis and since both of these processes serve antiviral functions, we examined the role RNase L may play in cell death. Inhibition of RNase L activity, by transfection with a dominant negative mutant, blocked staurosporine-induced apoptosis of NIH3T3 cells and SV40-transformed BALB/c cells, In addition, K562 cell lines expressing inactive RNase L were more resistant to apoptosis induced by decreased glutathione levels. Hydrogen peroxide-induced death of NIH3T3 cells did not occur by apoptosis and was not dependent upon active RNAse L. Apoptosis regulatory proteins of the Bcl-2 family did not exhibit altered expression levels in the absence of RNase L activity, RNase L is required for certain pathways of cell death and may help mediate viral-induced apoptosis.