Language:

TGFβ-activated Kinase 1 (TAK1) Inhibition by 5Z-7-Oxozeaenol Attenuates Early Brain Injury after Experimental Subarachnoid Hemorrhage

The Journal of biological chemistry, 2015-08, Vol.290 (32), p.19900-19909 [Peer Reviewed Journal]

2015 © 2015 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology. ;2015 by The American Society for Biochemistry and Molecular Biology, Inc. ;2015 by The American Society for Biochemistry and Molecular Biology, Inc. 2015 ;ISSN: 0021-9258 ;EISSN: 1083-351X ;DOI: 10.1074/jbc.M115.636795 ;PMID: 26100626

Full text available

Citations Cited by

Actions
1. Add to My Research
2. Remove from My Research
3. E-mail
4. Print
5. Permalink
6. Citation
7. EasyBib
8. EndNote
9. RefWorks
10. Delicious
11. Export RIS
12. Export BibTeX

Title:
TGFβ-activated Kinase 1 (TAK1) Inhibition by 5Z-7-Oxozeaenol Attenuates Early Brain Injury after Experimental Subarachnoid Hemorrhage
Author: Zhang, Dingding ; Yan, Huiying ; Li, Hua ; Hao, Shuangying ; Zhuang, Zong ; Liu, Ming ; Sun, Qing ; Yang, Yiqing ; Zhou, Mengliang ; Li, Kuanyu ; Hang, Chunhua
Subjects: 5Z-7-oxozeaenol ; Animals ; Anti-Inflammatory Agents, Non-Steroidal - pharmacology ; apoptosis ; Apoptosis - drug effects ; brain ; Cerebrovascular Trauma - genetics ; Cerebrovascular Trauma - metabolism ; Cerebrovascular Trauma - pathology ; Cerebrovascular Trauma - prevention & control ; Disease Models, Animal ; Gene Expression Regulation ; I-kappa B Proteins - antagonists & inhibitors ; I-kappa B Proteins - genetics ; I-kappa B Proteins - metabolism ; Injections, Intraventricular ; Male ; MAP Kinase Kinase 4 - antagonists & inhibitors ; MAP Kinase Kinase 4 - genetics ; MAP Kinase Kinase 4 - metabolism ; MAP Kinase Kinase Kinases - antagonists & inhibitors ; MAP Kinase Kinase Kinases - genetics ; MAP Kinase Kinase Kinases - metabolism ; mitogen-activated protein kinase (MAPK) ; Neurobiology ; Neurons - drug effects ; Neurons - metabolism ; Neurons - pathology ; neuroprotection ; Neuroprotective Agents - pharmacology ; NF-KappaB Inhibitor alpha ; NF-κB (NF-KB) ; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors ; p38 Mitogen-Activated Protein Kinases - genetics ; p38 Mitogen-Activated Protein Kinases - metabolism ; Phosphorylation ; Protein Kinase Inhibitors - pharmacology ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Stereotaxic Techniques ; subarachnoid hemorrhage ; Subarachnoid Hemorrhage - drug therapy ; Subarachnoid Hemorrhage - genetics ; Subarachnoid Hemorrhage - metabolism ; Subarachnoid Hemorrhage - pathology ; TAK1 ; Transcription Factor RelA - antagonists & inhibitors ; Transcription Factor RelA - genetics ; Transcription Factor RelA - metabolism ; Zearalenone - analogs & derivatives ; Zearalenone - pharmacology
Is Part Of: The Journal of biological chemistry, 2015-08, Vol.290 (32), p.19900-19909
Description: Accumulating evidence suggests that activation of mitogen-activated protein kinases (MAPKs) and nuclear factor NF-κB exacerbates early brain injury (EBI) following subarachnoid hemorrhage (SAH) by provoking proapoptotic and proinflammatory cellular signaling. Here we evaluate the role of TGFβ-activated kinase 1 (TAK1), a critical regulator of the NF-κB and MAPK pathways, in early brain injury following SAH. Although the expression level of TAK1 did not present significant alternation in the basal temporal lobe after SAH, the expression of phosphorylated TAK1 (Thr-187, p-TAK1) showed a substantial increase 24 h post-SAH. Intracerebroventricular injection of a selective TAK1 inhibitor (10 min post-SAH), 5Z-7-oxozeaenol (OZ), significantly reduced the levels of TAK1 and p-TAK1 at 24 h post-SAH. Involvement of MAPKs and NF-κB signaling pathways was revealed that OZ inhibited SAH-induced phosphorylation of p38 and JNK, the nuclear translocation of NF-κB p65, and degradation of IκBα. Furthermore, OZ administration diminished the SAH-induced apoptosis and EBI. As a result, neurological deficits caused by SAH were reversed. Our findings suggest that TAK1 inhibition confers marked neuroprotection against EBI following SAH. Therefore, TAK1 might be a promising new molecular target for the treatment of SAH. Background: Role of TGFβ-activated kinase 1 (TAK1) in the pathogenesis of early brain injury after subarachnoid hemorrhage (SAH) has not been reported. Results: TAK1 inhibition attenuates early brain injury and improves neurological deficits after SAH. Conclusion: TAK1 inhibition exhibits neuro-protective effects possibly through anti-apoptotic function. Significance: These results provide a novel target for SAH treatment.
Publisher: United States: Elsevier Inc
Language: English
Identifier: ISSN: 0021-9258
EISSN: 1083-351X
DOI: 10.1074/jbc.M115.636795
PMID: 26100626
Source: MEDLINE
PubMed Central
Alma/SFX Local Collection

Back to results list


INSPIRE LIBRARY - TON DUC THANG UNIVERSITY	(84-028) 37 755 057	Feedback
19 Nguyen Huu Tho St. Dist.7, HCM	thuvien@tdtu.edu.vn	Feedback

TGFβ-activated Kinase 1 (TAK1) Inhibition by 5Z-7-Oxozeaenol Attenuates Early Brain Injury after Experimental Subarachnoid Hemorrhage

Searching Remote Databases, Please Wait