[PMID]: | 29180011 |
[Au] Autor: | Inoue N; Hirouchi T; Kasai A; Higashi S; Hiraki N; Tanaka S; Nakazawa T; Nunomura K; Lin B; Omori A; Hayata-Takano A; Kim YJ; Doi T; Baba A; Hashimoto H; Shintani N |
[Ad] Endereço: | Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; Interdisciplinary Program for Biomedical Sciences, Institute for Academic Initiatives, Osaka University, 1-1 Yamadaoka, Suita, Osaka 565-0871, Japan; |
[Ti] Título: | Unbiased compound screening with a reporter gene assay highlights the role of p13 in the cardiac cellular stress response. |
[So] Source: | Biochem Biophys Res Commun;495(2):1992-1997, 2018 01 08. |
[Is] ISSN: | 1090-2104 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | We recently showed that a 13-kDa protein (p13), the homolog protein of formation of mitochondrial complex V assembly factor 1 in yeast, acts as a potential protective factor in pancreatic islets under diabetes. Here, we aimed to identify known compounds regulating p13 mRNA expression to obtain therapeutic insight into the cellular stress response. A luciferase reporter system was developed using the putative promoter region of the human p13 gene. Overexpression of peroxisome proliferator-activated receptor gamma coactivator 1α, a master player regulating mitochondrial metabolism, increased both reporter activity and p13 expression. Following unbiased screening with 2320 known compounds in HeLa cells, 12 pharmacological agents (including 8 cardiotonics and 2 anthracyclines) that elicited >2-fold changes in p13 mRNA expression were identified. Among them, four cardiac glycosides decreased p13 expression and concomitantly elevated cellular oxidative stress. Additional database analyses showed highest p13 expression in heart, with typically decreased expression in cardiac disease. Accordingly, our results illustrate the usefulness of unbiased compound screening as a method for identifying novel functional roles of unfamiliar genes. Our findings also highlight the importance of p13 in the cellular stress response in heart. |
[Mh] Termos MeSH primário: |
Glicosídeos Cardíacos/metabolismo Avaliação Pré-Clínica de Medicamentos/métodos Glicoproteínas/metabolismo Ensaios de Triagem em Larga Escala/métodos Chaperonas Moleculares/metabolismo Miócitos Cardíacos/metabolismo Estresse Oxidativo/fisiologia Mapeamento de Interação de Proteínas/métodos
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[Mh] Termos MeSH secundário: |
Genes Reporter Células HeLa Seres Humanos
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (Cardiac Glycosides); 0 (Glycoproteins); 0 (Molecular Chaperones); 0 (p13 glycoprotein, human) |
[Em] Mês de entrada: | 1802 |
[Cu] Atualização por classe: | 180214 |
[Lr] Data última revisão:
| 180214 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 171129 |
[St] Status: | MEDLINE |
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