دورية أكاديمية
Peptide OM-LV20 protects astrocytes against oxidative stress via the 'PAC1R/JNK/TPH1' axis.
| العنوان: | Peptide OM-LV20 protects astrocytes against oxidative stress via the 'PAC1R/JNK/TPH1' axis. |
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| المؤلفون: | Yin S; Department of Anatomy and Histology and Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, China., Pang A; Department of Neurology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China., Liu C; Department of Anatomy and Histology and Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, China., Li Y; Department of Anatomy and Histology and Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, China., Liu N; Department of Anatomy and Histology and Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, China., Li S; Department of Anatomy and Histology and Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, China., Li C; Department of Biochemistry and Molecular Biology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, China., Sun H; Department of Anatomy and Histology and Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, China., Fu Z; Department of Anatomy and Histology and Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, China., Wang Y; Department of Anatomy and Histology and Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, China., Zhang Y; Department of Anatomy and Histology and Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, China., Yang M; Department of Anatomy and Histology and Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, China. Electronic address: webfeng@126.com., Sun J; Department of Anatomy and Histology and Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, China., Wang Y; Key Laboratory of Chemistry in Ethnic Medicinal Resources & Key Laboratory of Natural Products Synthetic Biology of Ethnic Medicinal Endophytes, State Ethnic Affairs Commission & Ministry of Education, School of Ethnic Medicine, Yunnan Minzu University, Kunming, Yunnan, China. Electronic address: wangying_814@163.com., Yang X; Department of Anatomy and Histology and Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, China. Electronic address: yangxinwanghp@163.com. |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2022 Oct; Vol. 298 (10), pp. 102429. Date of Electronic Publication: 2022 Aug 28. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | Astrocytes*/drug effects , Astrocytes*/metabolism , Oxidative Stress*/drug effects , Peptides*/pharmacology , Stroke*/prevention & control , Tryptophan Hydroxylase*/metabolism , Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I*/metabolism , MAP Kinase Kinase 4*/metabolism, Animals ; Rats |
| مستخلص: | Stroke can lead to severe nerve injury and debilitation, resulting in considerable social and economic burdens. Due to the high complexity of post-injury repair mechanisms, drugs approved for use in stroke are extremely scarce, and thus, the discovery of new antistroke drugs and targets is critical. Tryptophan hydroxylase 1 (TPH1) is involved in a variety of mental and neurobehavioral processes, but its effects on stroke have not yet been reported. Here, we used primary astrocyte culture, quantitative real-time PCR, double immunofluorescence assay, lentiviral infection, cell viability analysis, Western blotting, and other biochemical experiments to explore the protective mechanism of peptide OM-LV20, which previously exhibited neuroprotective effects in rats after ischemic stroke via a mechanism that may involve TPH1. First, we showed that TPH1 was expressed in rat astrocytes. Next, we determined that OM-LV20 impacted expression changes of TPH1 in CTX-TNA2 cells and exhibited a protective effect on the decrease in cell viability and catalase (CAT) levels induced by hydrogen peroxide. Importantly, we also found that TPH1 expression induced by OM-LV20 may be related to the level of change in the pituitary adenylate cyclase-activating peptide type 1 receptor (PAC1R) and to the JNK signaling pathways, thereby exerting a protective effect on astrocytes against oxidative stress. The protective effects of OM-LV20 likely occur via the 'PAC1R/JNK/TPH1' axis, thus highlighting TPH1 as a novel antistroke drug target. Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: TPH1; astrocytes; ischemic stroke; peptide OM-LV20 |
| المشرفين على المادة: | 0 (OM-LV20) 0 (Peptides) EC 1.14.16.4 (tph1 protein, rat) EC 1.14.16.4 (Tryptophan Hydroxylase) 0 (Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I) EC 2.7.12.2 (MAP Kinase Kinase 4) |
| تواريخ الأحداث: | Date Created: 20220829 Date Completed: 20221114 Latest Revision: 20221130 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC9513268 |
| DOI: | 10.1016/j.jbc.2022.102429 |
| PMID: | 36037970 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1083-351X |
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| DOI: | 10.1016/j.jbc.2022.102429 |