Autophagy Upregulation and Apoptosis Downregulation in DAHP and Triptolide Treated Cerebral Ischemia
It has previously been demonstrated that ischemic stroke activates autophagy pathways; however, the mechanism remains unclear. The aim of this study is to further investigate the role that autophagy plays in cerebral ischemia. 2, 4-diamino-6-hydroxy-pyrimidine (DAHP), for its nitric oxide synthase (...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2015/120198 |
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| author | Yang Yang Keqiang Gao Zhiying Hu Weiyun Li Henry Davies Shucai Ling John A. Rudd Marong Fang |
| author_facet | Yang Yang Keqiang Gao Zhiying Hu Weiyun Li Henry Davies Shucai Ling John A. Rudd Marong Fang |
| author_sort | Yang Yang |
| collection | DOAJ |
| description | It has previously been demonstrated that ischemic stroke activates autophagy pathways; however, the mechanism remains unclear. The aim of this study is to further investigate the role that autophagy plays in cerebral ischemia. 2, 4-diamino-6-hydroxy-pyrimidine (DAHP), for its nitric oxide synthase (NOS) inhibiting neuroprotective effect, and triptolide (TP), for its anti-inflammatory property, were selected to administer pre middle cerebral artery occlusion (MCAO). The drugs were administered 12 hours prior to MCAO. Both magnetic resonance imaging (MRI) and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining showed that the drugs reduce the area of infarction. Immunoblotting analysis revealed increases in Beclin-1 and myeloid cell leukelia-1(Mcl-1) in treated rats. This could be a contributing factor to the reduction in autophagy induced damage. Immunochemistry and western blot showed that mTOR expression in treated rats was marginally different 24 h after injury, and this could also be significant in the mechanism. Furthermore, terminal deoxynucleotidyl transferase- (TdT-) mediated dUTP nick end labeling (TUNEL) staining proved that the drugs are effective in reducing apoptosis. The upregulation of Beclin-1 and Mcl-1 and downregulation of Bcl-2, caspase-3, and the Bcl-2/Beclin-1 ratio infer that the neuroprotective effect of DAHP and TP act via the mediation of autophagy and apoptosis pathways. |
| format | Article |
| id | doaj-art-dff58a0ba6e54e41897d14eaa8954242 |
| institution | OA Journals |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
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| series | Mediators of Inflammation |
| spelling | doaj-art-dff58a0ba6e54e41897d14eaa89542422025-08-20T02:21:07ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/120198120198Autophagy Upregulation and Apoptosis Downregulation in DAHP and Triptolide Treated Cerebral IschemiaYang Yang0Keqiang Gao1Zhiying Hu2Weiyun Li3Henry Davies4Shucai Ling5John A. Rudd6Marong Fang7Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou 310058, ChinaInstitute of Neuroscience, Zhejiang University School of Medicine, Hangzhou 310058, ChinaDepartment of Obstetrics and Gynecology, Hangzhou Red Cross Hospital, Hangzhou 310003, ChinaInstitute of Neuroscience, Zhejiang University School of Medicine, Hangzhou 310058, ChinaInstitute of Neuroscience, Zhejiang University School of Medicine, Hangzhou 310058, ChinaInstitute of Neuroscience, Zhejiang University School of Medicine, Hangzhou 310058, ChinaSchool of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong KongInstitute of Neuroscience, Zhejiang University School of Medicine, Hangzhou 310058, ChinaIt has previously been demonstrated that ischemic stroke activates autophagy pathways; however, the mechanism remains unclear. The aim of this study is to further investigate the role that autophagy plays in cerebral ischemia. 2, 4-diamino-6-hydroxy-pyrimidine (DAHP), for its nitric oxide synthase (NOS) inhibiting neuroprotective effect, and triptolide (TP), for its anti-inflammatory property, were selected to administer pre middle cerebral artery occlusion (MCAO). The drugs were administered 12 hours prior to MCAO. Both magnetic resonance imaging (MRI) and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining showed that the drugs reduce the area of infarction. Immunoblotting analysis revealed increases in Beclin-1 and myeloid cell leukelia-1(Mcl-1) in treated rats. This could be a contributing factor to the reduction in autophagy induced damage. Immunochemistry and western blot showed that mTOR expression in treated rats was marginally different 24 h after injury, and this could also be significant in the mechanism. Furthermore, terminal deoxynucleotidyl transferase- (TdT-) mediated dUTP nick end labeling (TUNEL) staining proved that the drugs are effective in reducing apoptosis. The upregulation of Beclin-1 and Mcl-1 and downregulation of Bcl-2, caspase-3, and the Bcl-2/Beclin-1 ratio infer that the neuroprotective effect of DAHP and TP act via the mediation of autophagy and apoptosis pathways.http://dx.doi.org/10.1155/2015/120198 |
| spellingShingle | Yang Yang Keqiang Gao Zhiying Hu Weiyun Li Henry Davies Shucai Ling John A. Rudd Marong Fang Autophagy Upregulation and Apoptosis Downregulation in DAHP and Triptolide Treated Cerebral Ischemia Mediators of Inflammation |
| title | Autophagy Upregulation and Apoptosis Downregulation in DAHP and Triptolide Treated Cerebral Ischemia |
| title_full | Autophagy Upregulation and Apoptosis Downregulation in DAHP and Triptolide Treated Cerebral Ischemia |
| title_fullStr | Autophagy Upregulation and Apoptosis Downregulation in DAHP and Triptolide Treated Cerebral Ischemia |
| title_full_unstemmed | Autophagy Upregulation and Apoptosis Downregulation in DAHP and Triptolide Treated Cerebral Ischemia |
| title_short | Autophagy Upregulation and Apoptosis Downregulation in DAHP and Triptolide Treated Cerebral Ischemia |
| title_sort | autophagy upregulation and apoptosis downregulation in dahp and triptolide treated cerebral ischemia |
| url | http://dx.doi.org/10.1155/2015/120198 |
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