Telomerase confers resistance to caspase-mediated apoptosis.
Telomerase confers resistance to caspase-mediated apoptosis.
复制标题
DOI：
10.2147/ciia.2006.1.2.155
复制
发表时间：
2006
影响因子：
3.6
通讯作者：
Kruk PA
中科院分区：
文献类型：
--
作者：
Bermudez Y;Erasso D;Johnson NC;Alfonso MY;Lowell NE;Kruk PA
越来越多的证据表明，加速端粒磨损和/或异常端粒酶活性有助于在许多疾病的发病机制。同样，人们越来越感兴趣的是开发新的疗法，以恢复或取代功能失调的细胞，其特征在于短端粒长度使用端粒酶阳性对应物或干细胞。虽然端粒酶从头添加端粒重复序列有助于增强增殖能力和寿命，但它也可以通过赋予对凋亡的抗性来增加细胞存活。因此，我们试图确定端粒酶参与卵巢表面上皮细胞减少凋亡。我们发现，端粒酶的催化成分hTERT的表达是足够的和特异性的，以减少半胱天冬酶介导的细胞凋亡。此外，hTERT表达降低了半胱天冬酶3、8和9的活化，降低了促凋亡线粒体蛋白t-BID、BAD和BAX的表达，并增加了抗凋亡线粒体蛋白Bcl-2的表达。端粒酶抑制半胱天冬酶介导的细胞凋亡的能力是p-jnk依赖性的，因为jip消除jnk表达会消除对细胞凋亡的抵抗。因此，这些发现表明端粒酶可能通过抑制JNK依赖的半胱天冬酶介导的细胞凋亡来促进上皮细胞的存活。
There is growing evidence that accelerated telomeric attrition and/or aberrant telomerase activity contributes to pathogenesis in a number of diseases. Likewise, there is increasing interest to develop new therapies to restore or replace dysfunctional cells characterized by short telomeric length using telomerase-positive counterparts or stem cells. While telomerase adds telomeric repeats de novo contributing to enhanced proliferative capacity and lifespan, it may also increase cellular survival by conferring resistance to apoptosis. Consequently, we sought to determine the involvement of telomerase for reduced apoptosis using ovarian surface epithelial cells. We found that expression of hTERT, the catalytic component of telomerase, was sufficient and specific to reduce caspase-mediated cellular apoptosis. Further, hTERT expression reduced activation of caspases 3, 8, and 9, reduced expression of pro-apoptotic mitochondrial proteins t-BID, BAD, and BAX and increased expression of the anti-apoptotic mitochondrial protein, Bcl-2. The ability of telomerase to suppress caspase-mediated apoptosis was p-jnk dependent since abrogation of jnk expression with jip abolished resistance to apoptosis. Consequently, these findings indicate that telomerase may promote cellular survival in epithelial cells by suppressing jnk-dependent caspase-mediated apoptosis.
登录
查看更多内容
影响因子：
3.3
作者：
Bachand, F;Boisvert, FM;Autexier, C
通讯作者：
Autexier, C
影响因子：
56.9
作者：
FENG, JL;FUNK, WD;VILLEPONTEAU, B
通讯作者：
VILLEPONTEAU, B
影响因子：
3.5
作者：
Cong, YS;Wen, JP;Bacchetti, S
通讯作者：
Bacchetti, S
影响因子：
64.5
作者：
Deng, YB;Ren, XY;Wu, XW
通讯作者：
Wu, XW
影响因子：
14.9
作者：
Fiset, S;Chabot, B
通讯作者：
Chabot, B