摘要
| 原文 | 英語 |
|---|---|
| 頁（從 - 到） | 5412-5423 |
| 頁數 | 12 |
| 期刊 | Nucleic Acids Research |
| 卷 | 39 |
| 發行號 | 13 |
| DOIs | |
| 出版狀態 | 已發佈 - 七月 2011 |
| 對外發佈 | Yes |
指紋
ASJC Scopus subject areas
- Genetics
引用此文
Translational and transcriptional control of Sp1 against ischaemia through a hydrogen peroxide-activated internal ribosomal entry site pathway. / Yeh, Shiu Hwa; Yang, Wen Bin; Gean, Po Wu; Hsu, Chung Yi; Tseng, Joseph T.; Su, Tsung Ping; Chang, Wen Chang; Hung, Jan Jong.
於: Nucleic Acids Research, 卷 39, 編號 13, 07.2011, p. 5412-5423.研究成果: 雜誌貢獻 › 文章
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TY - JOUR
T1 - Translational and transcriptional control of Sp1 against ischaemia through a hydrogen peroxide-activated internal ribosomal entry site pathway
AU - Yeh, Shiu Hwa
AU - Yang, Wen Bin
AU - Gean, Po Wu
AU - Hsu, Chung Yi
AU - Tseng, Joseph T.
AU - Su, Tsung Ping
AU - Chang, Wen Chang
AU - Hung, Jan Jong
PY - 2011/7
Y1 - 2011/7
N2 - The exact mechanism underlying increases in Sp1 and the physiological consequences thereafter remains unknown. In rat primary cortical neurons, oxygen-glucose deprivation (OGD) causes an increase in H2O2 as well as Sp1 in early ischaemia but apparently does not change mRNA level or Sp1 stability. We hereby identified a longer 5′-UTR in Sp1 mRNA that contains an internal ribosome entry site (IRES) that regulates rapid and efficient translation of existing mRNAs. By using polysomal fragmentation and bicistronic luciferase assays, we found that H2O2 activates IRES-dependent translation. Thus, H2O2 or tempol, a superoxide dismutase-mimetic, increases Sp1 levels in OGD-treated neurons. Further, early-expressed Sp1 binds to Sp1 promoter to cause a late rise in Sp1 in a feed-forward manner. Short hairpin RNA against Sp1 exacerbates OGD-induced apoptosis in primary neurons. While Sp1 levels increase in the cortex in a rat model of stroke, inhibition of Sp1 binding leads to enhanced apoptosis and cortical injury. These results demonstrate that neurons can use H2O2 as a signalling molecule to quickly induce Sp1 translation through an IRES-dependent translation pathway that, in cooperation with a late rise in Sp1 via feed-forward transcriptional activation, protects neurons against ischaemic damage.
AB - The exact mechanism underlying increases in Sp1 and the physiological consequences thereafter remains unknown. In rat primary cortical neurons, oxygen-glucose deprivation (OGD) causes an increase in H2O2 as well as Sp1 in early ischaemia but apparently does not change mRNA level or Sp1 stability. We hereby identified a longer 5′-UTR in Sp1 mRNA that contains an internal ribosome entry site (IRES) that regulates rapid and efficient translation of existing mRNAs. By using polysomal fragmentation and bicistronic luciferase assays, we found that H2O2 activates IRES-dependent translation. Thus, H2O2 or tempol, a superoxide dismutase-mimetic, increases Sp1 levels in OGD-treated neurons. Further, early-expressed Sp1 binds to Sp1 promoter to cause a late rise in Sp1 in a feed-forward manner. Short hairpin RNA against Sp1 exacerbates OGD-induced apoptosis in primary neurons. While Sp1 levels increase in the cortex in a rat model of stroke, inhibition of Sp1 binding leads to enhanced apoptosis and cortical injury. These results demonstrate that neurons can use H2O2 as a signalling molecule to quickly induce Sp1 translation through an IRES-dependent translation pathway that, in cooperation with a late rise in Sp1 via feed-forward transcriptional activation, protects neurons against ischaemic damage.
UR - http://www.scopus.com/inward/record.url?scp=80052226694&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80052226694&partnerID=8YFLogxK
U2 - 10.1093/nar/gkr161
DO - 10.1093/nar/gkr161
M3 - Article
C2 - 21441538
AN - SCOPUS:80052226694
VL - 39
SP - 5412
EP - 5423
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 13
ER -